Volume 181 Issue 6

We need a national tobacco act to regulate all aspects of tobacco manufacturing and marketing “Fire safe” cigarettes are those which self-extinguish when they are not being smoked, as opposed to regular cigarettes which continue to burn. For nearly two decades there has been opposition from the tobacco industry to proposals for legislation that would mandate fire-safe, or “reduced ignition propensity”, cigarettes. And this is despite the fact that smoking is the leading cause of residential and total fire deaths in at least eight countries, including Australia.1 The good news is that two jurisdictions in North America have now legislated to require all cigarettes to pass a “fire-safe” standard. Around 14 people in Australia die from cigarette-caused fires annually, and infants are over-represented in these deaths . . . The evidence that cigarettes cause fires is extensive. Data from the Australasian Fire Authorities Council (Mr C Donnelly, Director Corporate Strategy, New South Wales Fire Brigades, on behalf of the Australasian Fire Authorities Council, personal communication 5 February 2004) show that, annually, at least 4574 fires are caused directly by cigarettes and smokers’ materials around Australia (excluding the Northern Territory and South Australia, for which no data were available). In addition, an unknown proportion of another 78 894 fires of indeterminate origin could be associated with smoking. Determining the exact ignition source of a fire is often difficult because the evidence is generally destroyed. Cigarette butts are easily destroyed in fires, and conclusions about their role in causing fires are therefore deduced from a combination of evidence about the location and ignition point of fires (eg, beds, furniture, roadsides) and the elimination of other possible causes. The costs of cigarette-caused fires in terms of lives lost and property damaged are high. Around 14 people in Australia die from cigarette-caused fires annually,2 and infants are over-represented in these deaths, often dying in household fires resulting from cigarettes igniting bedding or furniture.3 In 1998–99, smoking-related fires throughout Australia cost some $52.1 million in tangible costs — health costs, private property damage and fire service costs — plus an estimated $28.5 million in intangible costs (such as the value of lives lost in such fires). This estimate is highly conservative, as it excludes valuations of public property damage, such as national parks, loss of animals, and of amenity while bushland regenerates.4 In Australia, particular focus has fallen on the role of discarded cigarettes as one cause of our infamous bushfires. Conservatively, it is estimated that about 7% of bushfires are caused by discarded cigarettes,5 and all states and territories now have laws for prosecuting people who discard lighted butts. A recent study has confirmed the ability of cigarettes to ignite bush litter. In outdoor conditions, with wind speed about 40 km/h, grassy fuel moisture content about 12% of oven dry weight, and humidity 14%, cigarette butts caused three ignitions in 75 trials (4%). If 1000 smouldering butts were discarded in comparable conditions, 40 fires might result.6 The same 2003 study examined butt discard rates on median strips next to two traffic lights on two of Sydney’s major arterial roads. Everyone’s daily experience of seeing people discarding glowing butts hardly needed confirmation, and the study found 426 discarded butts in a 3-week period.6 Education, fines, and talkback radio vilification of butt-throwers would thus appear to have minimal impact on this practice. Australian fire investigators report that hundreds of fire officers are often unnecessarily exposed to physical and psychological harm from cigarette-caused fires. Fire-cause investigators and other fire industry leaders unanimously support the introduction of regulations to reduce the fire risk of cigarettes.7 Tobacco companies commonly add burn accelerants, such as sodium and potassium citrate, to cigarette paper.8 However, in the United States, tobacco companies have patented many reduced ignition propensity cigarettes,9 and their own market research has shown them to be acceptable to smokers.10 To date only one such brand has been released (Philip Morris’s Merit, which is available in the USA and New Zealand). A recent comparative study of self-extinguishment showed that all regular manufactured cigarettes, 73% of Merit cigarettes, but no hand-rolled cigarettes (wrapped in virtually citrate-free paper), burnt full length.11 The hand-rolled cigarettes were wrapped in a brand of cigarette paper containing only trace levels of impregnated citrate. The elimination of citrate and other burning agents in cigarette paper thus appears to be a simple and effective means of dramatically reducing the ignition propensity of cigarettes. Now, after decades of advocacy from paediatricians, trauma physicians and fire authorities, both the state of New York and Canada have passed legislation on “fire-safe” cigarettes. From July this year, all cigarettes sold in the state of New York must pass a performance standard requiring that no more than 25% of cigarettes tested shall exhibit full-length burns on a bed of filter paper specified in the test method.12 (Merit would thus fail the New York standard.) Canada’s similar legislation was passed in March 2004, to take effect from October 2005.13 It would appear ethically inconceivable that the tobacco industry, knowing that it can produce products that will greatly reduce the potential to cause fires, should refuse to release them onto the market. Why, then, does it continue to do this, given the potential for saving lives, property and the likely public relations benefits to that beleaguered industry that would almost certainly follow? Evidence from internal tobacco company documents shows that the industry’s principal concerns appear to be legal — they are concerned about litigation relating to people burnt in fires caused by cigarettes that the industry could have made less combustive. As a 1983 British American Tobacco document stated: In view, however, of their recent decision taken by the Tobacco Institute not to work actively in the development of self-extinguishing cigarettes (for product liability reasons) it will be necessary for B&W management to define its wishes . . . [emphasis added].14 A major impediment to regulating fire-safe cigarettes in Australia is that the constituents of tobacco products are totally unregulated.15 Their ingredients and “quality” are not controlled by any food, pharmaceutical or poisons legislation, allowing the industry to avoid the sort of regulatory standards that could require cigarettes with reduced ignition propensity to conform to a standard. Instead, the industry enters into self-regulatory agreements with government, such as the current arrangement to list additives on industry websites. This agreement allows local manufacturers to avoid listing any ingredients they do not wish to reveal by designating them as generic “processing aids” or declaring them commercial-in-confidence.15 This regulatory “no-man’s land” should be replaced by a national tobacco act,16 which would allow complete regulation of all aspects of tobacco manufacturing and marketing. Such regulation, in mandating reduced ignition propensity cigarettes, would save lives, millions of dollars in damage and contribute to bushfire reduction. In the event that a national tobacco act was opposed by one or both of the major political parties, interim cigarette reduced ignition propensity regulations should be introduced, in line with those introduced in the Canadian and New York State jurisdictions.

Simon Chapman PhD · Antony Balmain

Altruism and trust lie at the heart of research on human subjects. Altruistic individuals volunteer for research because they trust that their participation will contribute to improved health for others and that researchers will minimise risks to participants. In return for the altruism and trust that make clinical research possible, the research enterprise has an obligation to conduct research ethically and to report it honestly. Honest reporting begins with revealing the existence of all clinical studies, even those that reflect unfavourably on a research sponsor’s product. Unfortunately, selective reporting of trials does occur, and it distorts the body of evidence available for clinical decision-making. Researchers (and journal editors) are generally most enthusiastic about the publication of trials that show either a large effect of a new treatment (positive trials) or equivalence of two approaches to treatment (non-inferiority trials). Researchers (and journals) typically are less excited about trials that show that a new treatment is inferior to standard treatment (negative trials) and even less interested in trials that are neither clearly positive nor clearly negative, since inconclusive trials will not in themselves change practice. Irrespective of their scientific interest, trial results that place financial interests at risk are particularly likely to remain unpublished and hidden from public view. The interests of the sponsor or authors notwithstanding, anyone should be able to learn of any trial’s existence and its important characteristics. The case against selective reporting is particularly compelling for research that tests interventions that could enter mainstream clinical practice. Rather than a single trial, it is usually a body of evidence, consisting of many studies, that changes medical practice. When research sponsors or investigators conceal the presence of selected trials, these studies cannot influence the thinking of patients, clinicians, other researchers, and experts who write practice guidelines or decide on insurance-coverage policy. If all trials are registered in a public repository at their inception, every trial’s existence is part of the public record and the many stakeholders in clinical research can explore the full range of clinical evidence. We are far from this ideal at present, since trial registration is largely voluntary, registry data sets and public access to them varies, and registries contain only a small proportion of trials. In this editorial, published simultaneously in all member journals, the International Committee of Medical Journal Editors (ICMJE) proposes comprehensive trials registration as a solution to the problem of selective awareness and announces that all eleven ICMJE member journals will adopt a trials-registration policy to promote this goal. The ICMJE member journals will require, as a condition of consideration for publication, registration in a public trials registry. Trials must register at or before the onset of patient enrolment. This policy applies to any clinical trial starting enrolment after 1 July 2005. For trials that began enrolment before this date, the ICMJE member journals will require registration by 13 September 2005 before considering the trial for publication. We speak only for ourselves, but we encourage editors of other biomedical journals to adopt similar policies. For this purpose, the ICMJE defines a clinical trial as any research project that prospectively assigns human subjects to intervention or comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Studies designed for other purposes, such as to study pharmacokinetics or major toxicity (eg, phase I trials), would be exempt. The ICMJE does not advocate one particular registry, but its member journals will require authors to register their trial in a registry that meets several criteria. The registry must be accessible to the public at no charge. It must be open to all prospective registrants and managed by a not-for-profit organisation. There must be a mechanism to ensure the validity of the registration data, and the registry should be electronically searchable. An acceptable registry must include at minimum the following information: a unique identifying number, a statement of the intervention (or interventions) and comparison (or comparisons) studied, a statement of the study hypothesis, definitions of the primary and secondary outcome measures, eligibility criteria, key trial dates (registration date, anticipated or actual start date, anticipated or actual date of last follow-up, planned or actual date of closure to data entry, and date trial data considered complete), target number of subjects, funding source, and contact information for the principal investigator. To our knowledge, at present, only www.clinicaltrials.gov, sponsored by the United States National Library of Medicine, meets these requirements; there may be other registries, now or in the future, that meet all these requirements. Registration is only part of the means to an end; that end is full transparency with respect to performance and reporting of clinical trials. Research sponsors may argue that public registration of clinical trials will result in unnecessary bureaucratic delays and destroy their competitive edge by allowing competitors full access to their research plans. We argue that enhanced public confidence in the research enterprise will compensate for the costs of full disclosure. Patients who volunteer to participate in clinical trials deserve to know that their contribution to improving human health will be available to inform healthcare decisions. The knowledge made possible by their collective altruism must be accessible to everyone. Required trial registration will advance this goal.

Catherine De Angelis MD · Jeffrey M Drazen MD · Frank A Frizelle MB ChB · Charlotte Haug MD · John Hoey MD · Richard Horton · Sheldon Kotzin · Christine Laine MD, MPH · Ana Marusic MD, PhD · A J P M Overbeke MD, PhD · Torben V Schroeder MD, DMSc · Hal C Sox MD · Martin B Van Der Weyden MD, FRACP, FRCPA

The benefits of whole-body CT screening need to be carefully weighed against the risks Whole-body computed tomography (CT) screening is currently marketed to asymptomatic individuals as a form of proactive and preventive healthcare. Commonly, the chest, abdomen and pelvis are scanned, but the head and neck are also included in the “five-region” scans offered by some commercial companies. In the United States, it has been estimated that, over the past 3 years, 15 million whole-body scans have been performed in about 400 centres.1 In Australia, clinics in Brisbane and Sydney are offering whole-body CT screening. Despite the growth in demand for whole-body scans, there is no evidence that they are effective in detecting serious, treatable disease without undue cost or undesirable effects. The value of many applications of imaging technology for diagnosing and monitoring disease and planning treatment is accepted. But sceptics of whole-body screening note the lack of evidence of benefit, the likelihood of clinically unimportant findings that may result in possibly needless further investigations, and the risks of radiation. There have been no published studies of the safety or efficacy of whole-body screening. In Australia, we identified only one ongoing study: researchers at the University of New South Wales are currently assessing 1500 people who have had whole-body CT scans, measuring significant pathological findings and their eventual outcomes (Fred Ehrlich, Professor of Public Health and Community Medicine, University of NSW, personal communication). The prevalence of findings on whole-body CT is high. In a recent conference presentation, it was reported that, of 1200 whole-body CT scans, 87% showed at least one finding, and nearly a third of patients were advised to undergo further testing or follow-up.2 In a study using CT to screen for lung cancer,3 700 ancillary findings (not related to lung cancer) were noted in about 1520 screened individuals. Most were false-positive results, and the follow-up adversely affected the patients’ quality of life and resulted in unnecessary diagnostic and interventional procedures.3 It has been estimated that, in healthy people, about 80% of abnormalities detected on CT screening studies may not be life-threatening;4 however, this estimate requires confirmation. Follow-up of non-significant findings has health, psychosocial and cost implications. In Australia, Medicare and private health insurance agencies do not cover the costs of a whole-body scan (currently over $800), but may reimburse follow-up diagnostic evaluations. What are the risks of whole-body screening? The radiation exposure has been estimated to be somewhere between 1 and 24 mSv per CT scan.5,6 However, owing to technical and anatomical factors, the dose can vary by a factor of 10 or more between patients.6 A 10 mSv radiation exposure is associated with an increased risk of fatal cancer of about 1 in 2000 (this can be compared with a lifetime risk of about 1 in 5).6 If screening were undertaken in Australia at 3-year intervals, the risk of radiation-related death would be an estimated 0.4%, 0.3% and 0.1% for men starting screening at 40, 50 and 60 years, respectively, and 0.6%, 0.4% and 0.2% for their female counterparts.7 Compared with 10 other types of x-ray, CT scans are responsible for the largest number of radiation-induced cancers per year in nine cancer sites examined.8 In Australia, the Radiation Advisory Council and the NSW Environment Protection Authority concluded in 2003 that whole-body screening by CT is inappropriate for the general diagnosis of healthy individuals. Similarly, the Royal Australian and New Zealand College of Radiologists and the Radiation Health and Safety Advisory Council have each published statements indicating that there is insufficient scientific evidence to support whole-body CT screening in asymptomatic patients with no family history suggesting disease.9,10 In the United States, several professional groups, including the American College of Radiology and the American Association of Physicists in Medicine, do not recommend whole-body CT screening for asymptomatic healthy individuals.11,12 In New South Wales, it has been illegal since 2003 to perform a whole-body CT scan without a written request from an independent medical practitioner. The radiation dose and health risks involved must be fully explained, individuals under the age of 50 must be told that they are more at risk of developing cancer as a result of the procedure, and written and informed consent must be obtained before the scan can be performed.13 Breaches of these new regulations may attract fines of up to $27 500 for individuals, $165 000 for corporations and/or a maximum of two years’ imprisonment.13 This approach disallows self-referral. We made enquiries to medical defence providers and professional organisations regarding the referral of asymptomatic patients for whole-body CT screening. One medical indemnity provider indicated that, in the event of an untoward incident, members would not be indemnified if they practised whole-body CT screening for asymptomatic patients or referred patients using particular referral formats supplied by commercial CT screening companies. We suggest that practitioners check with their own indemnity provider regarding their coverage under these circumstances. The key question is whether whole-body CT screening will lead to detection of unsuspected diseases, resulting in earlier treatment and improved outcomes, or simply reveal abnormalities for which follow-up and treatment will result in no overall gain. This question can only be answered with well designed studies. In the interim, the community interest in whole-body CT screening is growing, and GPs, especially, may be put in a difficult position by patients requesting a referral for a whole-body scan. Some Internet sources of information on whole-body CT screening are listed in the Box. Consumers and medical practitioners need to be wary of the many claims that are made in support of whole-body CT screening for early disease. Guidelines — based on the current evidence of benefits and risks of whole-body CT screening, assessed by reputable professional and consumer bodies — would be valuable to assist the decisions of both medical practitioners and consumers and to provide a better basis for informed consent. In conclusion, the current evidence suggests that patients should be advised that there is no proven benefit, and indeed possible detriment, from undertaking whole-body CT screening. Internet sources of information on whole-body computed tomography Australian professional and government organisations Royal Australian and New Zealand College of Radiologists www.ranzcr.edu.au/open/policies/diagnostic_imaging/pol2_2.htm Radiation Health and Safety Advisory Council www.arpansa.gov.au/pubs/rhsac/st1_aug02.pdf NSW Environment Protection Authority www.epa.nsw.gov.au/radiation/ctbodyscans.htm NSW Health www.ppc.health.nsw.gov.au/news/2002/September/26-09-02ct.htm www.health.nsw.gov.au/news/2003/June/08-06-03ct.htm www.chs.health.nsw.gov.au/pubs/factsheet/pdf/body_scan_fs.pdf International professional organisations US Food and Drug Administration wwwfda.gov/cdrh/ct American College of Radiology www.acr.org/departments/pub_rel/press_releases/total-bodyCT.html Health Physics Society hps.org/documents/CTPosStm.pdf Other sources of information your patients may be using Life Span Medical Imaging www.lifespanmedical.com.au Total Health Screening www.totalhealthscreening.com.au Health Imaging CT www.openmrimgt.com/healthscreen/index.htm Be Well Body Scan www.bewellbodyscan.com Full Body Scanning www.fullbodyscanning.com/sanfrancisco/full-body-scan.jsp The Oprah Winfrey Show www.oprah.com/tows/pastshows/tows_2000/tows_past_20001002_b.jhtml www.oprah.com/tows/pastshows/tows_2000/tows_past_20001002_c.jhtml

Cleola Anderiesz PhD, BSc · J Mark Elwood MD, DSc · Brian R McAvoy MD, FRACGP, FRCP · Lizbeth M Kenny MB BS, FRANZCR

More than 170 clinicians from diverse healthcare backgrounds attended the National Institute of Clinical Studies (NICS) “Heart Failure Forum 2004: improving outcomes in chronic care”, held in Canberra, 7–8 June 2004. The purpose of the forum was to raise awareness of the growing burden of heart failure, engage with Australian and international experts in heart failure and chronic care management, and explore strategies for improving outcomes in chronic care. Successful models of careGeoffrey Tofler (Chair of the NICS Heart Failure Advisory Group and Professor of Preventive Cardiology, University of Sydney) set the scene by highlighting gaps in the current medical treatment of heart failure. These gaps are most notable in the use of evidence-based drug therapies, such as angiotensin-converting enzyme (ACE) inhibitors and β-blockers, that reduce symptoms and hospital admissions and improve survival.1 Chronic care expert Ed Wagner (Director, MacColl Institute for Healthcare Innovation, Group Health Cooperative, Seattle, Washington, US, and leader of the Robert Wood Johnson Foundation Improving Chronic Illness Care Program) argued that the current care system is not working adequately for either patients or healthcare professionals,2 and emphasised the importance of redesigning care systems around the needs of patients with chronic illnesses. He described the essential elements of the chronic care model (Box 1),3 and illustrated how the model, combined with the Institute of Healthcare Improvement collaborative improvement method, enabled over 1000 US healthcare organisations to improve quality of care for patients with asthma, diabetes and chronic heart failure.4 Peter Didsbury (Chairman, New Zealand Guidelines Group, and Deputy Head and Manager of Integration, ProCare Health Ltd, Wellington, NZ) reported increased prescribing of ACE inhibitors, β-blockers and spironolactones following multifaceted intervention strategies, such as improved access to echocardiography, rapid access to cardiology advice, funding for β-blocker titration, access to a cardiac nurse specialist and 24-hour telephone triage. The results of an unpublished randomised trial he conducted involving patients with chronic obstructive pulmonary disease led him to suggest that improving the effectiveness of patient adherence through more structured care processes (such as holistic assessments, education about the condition, lifestyle therapy, action plans and active follow-up) may have greater effect. The vital role played by nursing staff was highlighted by Simon Stewart (Chair, Cardiovascular Nursing, and Director of the Centre for Innovation in Health, University of South Australia). He presented evidence from a recent systematic review of randomised trials of multidisciplinary strategies for the management of patients with heart failure at high risk for admission. This review showed that programs that incorporate follow-up by a specialised multidisciplinary team (in either a clinic or a non-clinic setting) reduce mortality, heart failure hospitalisations and all-cause hospitalisations.5 Stewart emphasised the need for a more systematic implementation of specialist nurse-led, home-based, follow-up services after discharge for patients with heart failure. Such services are currently available to less than 10% of those needing them. Whether this form of care is applicable in rural and remote locations is not certain, according to Henry Krum (Director, NHMRC Centre of Clinical Research Excellence in Therapeutics, Monash University), who described the computerised, telephone-based patient support system (“Telewatch”) his research group is trialling in Australia. The system allows healthcare providers to closely monitor symptoms of patients with chronic heart failure and to track progress, respond to deterioration and make suggestions to improve overall management. Specific questions relate to diet, exercise, alcohol use, smoking, use of drugs for chronic heart failure, use of prescribed and over-the-counter medications unrelated to chronic heart failure, mood state and current coping. Results are expected by the end of 2005. The role of GPs in management of heart failureAlthough heart failure is a leading medical cause of hospital admissions in older people, Justin Beilby (Head, Department of General Practice, University of Adelaide) noted that patients with heart failure represent a low proportion of the total patients that each general practitioner treats. Of concern to GPs is the need to identify people with early heart failure, who would benefit from more aggressive intervention. This point was reinforced by Michael Feneley (Chair, Cardiac Society of Australia and New Zealand Echocardiography Working Group), who stressed that new shortness of breath with no other obvious cause is often a symptom of early heart failure and should trigger investigation. He believes echocardiography is the most useful investigation in confirming or ruling out heart failure and is critical for determining the underlying cause and guiding therapy.6 Mark Harris (Professor, General Practice, University of New South Wales) detailed the important role of Divisions of General Practice in providing support and feedback to practices in the collection and analysis of data and in the use of patient registries — key elements of proactive chronic care patient management. The forum heard from Judith Mackson (Prescribing Program Coordinator, National Prescribing Service [NPS]) that the NPS, the National Heart Foundation of Australia (NHFA) and the NICS have formed a collaboration to improve targeted elements of heart failure diagnosis and management in general practice. This joint program will deliver key messages on drug use for treating heart failure and will emphasise the importance of echocardiography to confirm the diagnosis and guide treatment. Current government initiatives in chronic careThe importance of adopting a more systematic approach to chronic care management in Australia was reinforced by Andrew Tonkin (Director, Health, Medical and Scientific Affairs, NHFA), who argued that the effective management of heart failure represents an excellent paradigm for improving the care of people with other chronic conditions. The value and cost-effectiveness of management programs that can support patients with heart failure in the home and community and prevent hospitalisation have been demonstrated. Programs and information systems for patients with heart failure, once established, could be easily adapted to the needs of other chronically ill patients. Jane Halton (Secretary, Australian Government Department of Health and Ageing) highlighted recent Budget initiatives. Funding is provided for 1600 more primary care nurses and a new Medicare Benefits Schedule item number linked to the Enhanced Primary Care multidisciplinary care plan for services provided by allied health professionals. Ms Halton outlined the government’s plans for a national chronic disease strategy, following development and consultations by the National Health Priority Action Council’s Chronic Disease Strategy Group. The forum heard about different state heart failure programs. Craig White (Deputy Chair, Victorian Hospital Admission Risk Prevention Program, and Executive Director, Clinical Services, Austin Health) and Kym Scanlon (Assistant Director, Chronic Care Program, NSW Health) presented figures showing encouraging reductions in hospital admissions for chronic heart failure since the commencement of statewide chronic care programs, such as the Victorian Hospital Admission Risk Prevention Program and the NSW Chronic and Complex Care Program.7,8 Clearly, more patients need to access these programs, with only an estimated 15% of eligible patients enrolled in Victoria (Andrea Driscoll, Deakin University). NSW Health is currently addressing implementation and spread of issues through a statewide chronic care collaboration that focuses on heart failure and chronic obstructive pulmonary disease. The change principles of the collaboration are based on the key elements of Wagner’s chronic care model, as well as policy components from the World Health Organization’s Innovative Care for Chronic Conditions Framework.9 Conclusion and the way forwardIn the concluding plenary session, Didsbury and Wagner suggested strategies that would facilitate implementation of the chronic care model in Australia. They emphasised the need to reward care planning, support efforts to encourage practice system change, and make patients a part of the planning. Using the patient journey as a framework, Geoffrey Tofler presented a matrix of key strategies and interventions that patients, clinicians and governments should consider to improve outcomes and quality of life for patients with heart failure (Box 2). The matrix indicates areas where best-practice models of care are known, such as cardiac nurse specialists for post-discharge heart failure patients, and areas where more research is needed, such as the best use of practice nurses in chronic diseases. Finally, the matrix suggests areas where enhanced government support is needed (such as in creating mechanisms for funding comprehensive care programs and in further funding for practice nurses). The range of participants at the forum reinforced the broad approach needed to improve outcomes in heart failure. Furthermore, strategies adopted successfully with heart failure could have major effects when extrapolated to other chronic conditions. The forum presentations and a more detailed report are available on the National Institute of Clinical Studies website (www.nicsl.com.au). 1 The chronic care model Source: Ed Wagner keynote address, NICS Heart Failure Forum 2004. Available at www.nicsl.com.au. For more information on the chronic care model, see reference 3. 2 Matrix of key strategies and interventions for a patient with heart failure Stage Prevention Early stage Acute exacerbation Ongoing care Palliative care Issues Identification of high-risk patients Recognition of early signs and symptoms, when and whom to refer for echocardiography Use and availability of echocardiography, particularly in rural areas Use of BNP in primary care to be further defined In-hospital initiation of appropriate therapy and discharge to community with management plan, including dose titration schedules Comorbidities, diagnostic issues, systematic patient education and support Need research on the education of practice nurses in chronic care management and effectiveness in improving patient outcomes Changing roles in general practice Need research on access to palliative care services and how to extend these to patients with heart failure Model Prevention and management of coronary artery disease and hypertension Consumer Education (NICS Online directory of quality information for patients with heart failure) Appropriate use of echocardiography in diagnosis and assessment of heart failure in primary care (NICS education module in preparation) Clinician-led quality improvement programs Heart failure nurse-led, home-based management programs (Alternatives include hospital-based rehabilitation, heart failure clinics) Chronic care management model Study and implement self-management models Targeted interventions aimed at implementing best practice management of heart failure in primary care (NICS, NPS and NHFA joint heart failure program) Need research on appropriate palliative care model and extrapolation of palliative care and nursing principles Consumer role Awareness of risk factors (SNAP) Awareness of early symptoms and precipitants, especially in high risk individuals Working in partnership with healthcare professionals Access to self-management education and support, particularly post-discharge Self-management education and support, ongoing monitoring, adherence to treatment Heart Failure Action plan Consider advance directives Access to self-management and support Provider role Identification and treatment of high-risk patients by GPs, cardiologists, general physicians Assessment of patients with early signs and symptoms by GPs Referrals to cardiologists or general physicians, where appropriate Emergency physicians, cardiologists, general physicians, geriatricians, cardiac nurses, hospital pharmacists GPs, practice nurses with training in chronic care and support from cardiac nurses, allied health, community nurses and pharmacists GPs, community nurses, palliative care teams Government role Heart failure health promotion campaign, and systems in place to support this Access to echocardiography, access to cardiologists Need heart failure prevalence study and minimum heart failure dataset Need initiatives for improved outcomes for cardiovascular disease in primary care Ongoing resourcing for cardiac nurse role in acute settings and post-discharge (state) Testing and implementation of chronic care model in general practice and system redesign issues (Commonwealth) Mechanism for funding comprehensive care programs More practice nurses Capacity building for quality improvement Extend palliative care entitlements to patients with heart failure (eg, access to medicines, oxygen and home nursing services) BNP = Brain natriuretic peptide. NICS = National Institute of Clinical Studies. NPS = National Prescribing Service. NHFA = National Heart Foundation of Australia. SNAP = Smoking, Nutrition, Alcohol, Physical activity.

Susan M Phillips DPhil · Janice M Davies PhD · Geoffrey H Tofler MB BS, MD

Objective: To assess the effect of a restriction on publicly subsidised temazepam 10 mg capsules upon the injection of benzodiazepines by injecting drug users (IDUs).Design and participants: Cross-sectional study of regular IDUs targeting periods before and after the policy change. Analysis of prescription data, including time-series analysis.Setting: Drug services in the capital cities of New South Wales, Victoria, Tasmania, Queensland and the Northern Territory.Main outcome measures: Changes in prescriptions and patterns of benzodiazepine use; harms associated with benzodiazepine use.Results: There was a decrease in temazepam 10 mg capsule prescriptions and a corresponding increase in temazepam 10 mg tablet prescriptions after the policy change. IDU survey data suggested that IDUs continued to inject benzodiazepines and temazepam capsules. The frequency of the injection of capsules after the restriction appeared similar to that before the policy change. There was no change in the frequency of injection of tablets. Most IDUs reported obtaining their benzodiazepines from doctors, with substantial proportions obtaining capsules even after the restriction. About half the IDUs reported purchasing benzodiazepines on the street. Most IDUs who injected benzodiazepines reported injection-related problems.Conclusion: Limiting the prescribing of temazepam capsules may have reduced their injection by some IDUs, but additional strategies are needed to reduce the misuse among this group. These may include further restriction of capsule preparations, continued education of doctors and IDUs, and the examination of prescribing practices of individual doctors.

Courtney L Breen MPH(Hons), GradDipSc(Psych), BSc · Louisa J Degenhardt PhD, BSc(Hons) · Amanda D Roxburgh BAHons(Psych), MCrim · Raimondo B Bruno BSc(Hons) · Rebecca Jenkinson BEng(Geo), GradDipEpiBiostats

Objectives: To review changes in patterns of care for women with early invasive breast cancer in Western Australia from 1989 to 1999, and compare management with recommendations in the 1995 National Health and Medical Research Council guidelines.Design and setting: Population-based surveys of all cases listed in the Western Australian Cancer Registry and Western Australian Hospital Morbidity Data System.Main outcome measures: Congruence of care with guidelines.Results: Data were available for 1649 women with early invasive breast cancer (categories pT1or pT2; pN0 or pN1; and M0). In 1999, 96% had a preoperative diagnosis by fine-needle aspiration or core biopsy (compared with 66% in 1989), with a synoptic pathology report on 95%. Breast-conserving surgery was used for 66% of women with mammographically detected tumours (v 35% in 1989) and 46% of those with clinically detected tumours (v 28% in 1989), with radiotherapy to the conserved breast in 90% of these cases (83% in 1989). Adjuvant chemotherapy was given to 92% of premenopausal women with node-positive disease and 63% with poor-prognosis node-negative tumours (v 78% and 14%, respectively, in 1989). Among postmenopausal women with receptor-positive tumours, tamoxifen was prescribed for 91% of those with positive nodes (85% in 1989) and 79% of those with negative nodes (30% in 1989). Among postmenopausal women with receptor-negative tumours, chemotherapy was prescribed for 70% with positive nodes (v 33%) and 58% with negative nodes (v none).Conclusions: Patterns of management of women with early invasive breast cancer in Western Australia during the 1990s changed significantly in all respects toward those recommended in the 1995 guidelines.

Suzanne P McEvoy MAppEpid, FAFPHM · Claire Haworth RN · Jennett M Harvey FRCPA · Lin Fritschi PhD, FAFPHM · David M Ingram MS, FRACS · Michael J Byrne BMedSci, FRACP · Joanna Dewar FRACP · David J Joseph FRANZCR · James Trotter MD, FRACP · Chris Harper FRANZCR · Greg F Sterrett FRCPA, FIAC · Konrad Jamrozik DPhil, FAFHM

Objective: To identify deaths in Australasia associated with overdose of γ-hydroxybutyrate (GHB) and its precursors (γ-butyrolactone and 1,4-butanediol).Design: A retrospective search of medical and scientific information sources, as well as popular newsprint, for the period January 2000 – August 2003, with formal clinical, toxicological and forensic evaluation of retrieved data.Main outcome measure: Death associated with forensic data implicating GHB or its analogues.Results: Ten confirmed GHB-associated deaths were identified, with eight considered to be directly attributable to GHB. Only two of these eight cases were positive for ethanol toxicology.Conclusions: Our study supports the existing evidence that GHB overdose is associated with fatalities, and that fatal overdoses occur in the context of isolated use.

David G E Caldicott BSc(Hons), MB BS · Fiona Y Chow MB BS, FACEM · Brian J Burns MB BCh, BAO, MRCSEd(A · Peter D Felgate BSc(Hons) · Roger W Byard MB BS, MD, FRCPath

Raised plasma homocysteine (tHcy) concentrations are caused by genetic mutations, vitamin deficiencies, renal and other diseases, numerous drugs, and increasing age. Raised tHcy concentrations are associated with laboratory evidence of atherogenesis (eg, endothelial dysfunction) and thrombosis, and epidemiological evidence of an increased risk of atherothrombotic vascular disease. An association between raised tHcy concentration and an increased risk of atherothrombosis is independent of other vascular risk factors, strong, dose-related and biologically plausible, but has not been proven to be causal in randomised controlled trials. A recent trial identified no significant benefit from lowering tHcy concentration by folic-acid-based multivitamin therapy among 3680 patients with recent ischaemic stroke, but did not reliably exclude a modest but important reduction in the relative risk of stroke of up to 20%; a difference of only 2 mmol/L in tHcy concentration between the two treatment groups was probably due to widespread vitamin use and fortification of grains and staple foods with folate in North America. There is currently insufficient evidence to recommend routine screening and treatment of high tHcy concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease.

Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MSc, FRACP, FRCPA · Wai Khoon Ho MB ChB, FRACP, FRCPA · Frank M van Bockxmeer PhD, FAHA

The case of a 13-year-old girl given permission by the Family Court of Australia to begin a sex-change process involves complex issues. Nevertheless, the ethical justification for the decision is not complicated. In this case, it can be argued that the net benefit eclipses concerns about competence, autonomy and the appropriateness of the intervention. The debate this case generated in the media reminds us that one of the essential tasks in ethics debates is to get our facts straight. In a landmark judgment, the Chief Justice of the Family Court of Australia has given permission for a 13-year-old girl to begin a sex-change process. The biologically normal girl, referred to in the judgment as “Alex” or “he”, has been diagnosed with a gender-identity disorder and has experienced major depression, self-harming behaviour and suicidal thoughts.1* Gender-identity disorders, sometimes referred to as “gender dysphoria” (“dysphoria” indicating distress)5 or “transsexualism”, are rare and complex conditions in children and adolescents. According to a Royal College of Psychiatrists report,6 they are often associated with emotional and behavioural difficulties and involve psychological, biological, family and social issues. In the course of psychosexual development, the young person “experiences their phenotypic sex as incongruous with his or her own sense of gender identity”, and adolescents with this condition often experience intense distress. The majority of affected children eventually develop a homosexual orientation, but the outcome is not easily predicted. Only a small proportion become transsexuals or transvestites.6 In the present case, Alex has had a strong, longstanding desire to live as a male and become male in appearance and has gone to distressing lengths to conceal his female body. For example, to avoid having to use the female toilets, he started wearing nappies to school and would not drink liquids.1 Alex’s past life has been troubled. His father, with whom he was very close, died suddenly when Alex was young, and his mother rejected him. He now lives with an aunt. The proposed treatmentGender reassignment is a staged process. The proposed treatment for Alex involves, firstly, the continuous administration of a combination of oestrogen and progestogen that is a form of the contraceptive pill. The goal of this stage is solely to suppress menstruation, and the effects are “completely reversible”.1 The second stage of treatment for Alex involves hormone therapy with a luteinising-hormone-releasing-hormone analogue (to suppress the pituitary–ovarian axis) and testosterone; this can begin in 3 years’ time, at age 16, if Alex still wants to be a boy. Some changes with this stage of the treatment are irreversible. Changes include masculinisation of the voice, muscle growth, increase in facial and body hair, growth of the clitoris and behavioural effects.1 Surgery would complete the sex-change process; however, surgical intervention was not sought or contemplated in the court application. The Chief Justice authorised the stages of the proposed treatment as a “single package of reversible and irreversible treatment”, but the only aspect that will take immediate effect is administration of the contraceptive pill.1 Although Alex and his doctors have authorisation to commence the irreversible hormone therapy, surgical intervention is not part of that “package”. Alex would not be eligible for surgical intervention until he is at least 18 years old.1 From the age of 18, however, he will be legally entitled to make his own decisions. The legal basis of the decisionUnder the Family Law Act 1975 (Cwlth), the Family Court is required to “regard the best interests of the child as paramount”.1 The Chief Justice in this case based his decision on the High Court’s decision in Marion’s case.7 Matters to be considered include the particular condition of the child; the nature of the proposed treatment; reasons for the proposed treatment; alternative courses of treatment; desirability and effect of the proposed treatment compared with alternatives; physical, psychological and social implications of authorising or not authorising the proposed treatment; the nature and degree of any risk associated with authorising or not authorising the proposed treatment; and the views of the child’s guardian(s) and of the child.1 The Court was making the decision not because Alex lacked sufficient maturity and understanding or because he was a ward of the state. The permission of the Family Court was required because the proposed treatment was not considered a treatment for a “malfunction” or a “disease”.1 The “irreversible” element of the intervention, with accompanying “significant risk”, means that it falls into the legal category of “special medical procedures” — cases requiring court authorisation.1,8 Public debate generated by the decisionThe Court’s decision to allow the sex-change process has sparked public debate and provoked strong reactions in the media. Bioethicist Nicholas Tonti-Filippini has condemned the decision as “unbelievable” and called on the government to intervene. He argues that “all the evidence suggests that gender dysphoria is a form of mental illness and should be treated as a mental illness, not by trying to adjust her biologically to match the delusion”.9,10 Another critic claims that allowing the 13-year-old to begin the sex-change process is colluding with the fantasy rather than treating the condition — “like allowing a child who imagines he is a horse to undergo transformative surgery”.11 Some challenge the diagnosis and the proposed treatment by arguing that we should view Alex as a victim of emotional and psychological abuse: “We have a terrible feeling that Alex may have received too much intervention of the wrong kind, too soon.”12 Others have stated, “It’s her troubled mind we must work on, not her healthy body”,13 and “She is much, much too young to make this decision”.10 Some also worry that Alex will come to regret his decision.14,15 The competence of a 13-year-old to make this kind of decision and the implications of making competence determinations have also been debated. One newspaper editorial has called the Court’s decision “troubling”, because “it is a fair bet that what Alex wants now above all else may not be her heart’s desire in five, let alone 10 years’ time”.16 Another editorial claims that adolescent unhappiness cannot be measured from an adult’s perspective, and warns that “anyone who must deal with an adolescent’s misery needs to consider very carefully what the consequences of disregarding it may be”.17 Few commentators have come out in defence of the Court’s decision, but a spokesperson for the Australian and New Zealand College of Psychiatrists has said that the judgment was important “because it acknowledged the severity of Alex’s condition and allowed the appropriate treatment”.18 A representative of TransGender Victoria commended the decision, because adolescence is “the worst time” for people with gender-identity problems committing suicide.10 Identifying the issues of concern and assessing the debateThe overriding concern in this debate seems to be the possibility of harm. Some view the proposed medical treatment as inappropriate or premature and fear that Alex may later regret undergoing the treatment. Others think that the treatment offers relief and that withholding it would cause great harm. The competence of a young person to make this kind of decision, the goals of the intervention, and whether the end justifies the means also figure in the debate. An essential task of ethicsFirst of all, this case demonstrates one of the essential tasks of ethics — getting our facts straight. Some commentators who oppose the Court’s decision may have concluded that surgery is part of the proposed treatment or that surgery is inevitable. But this is not the case. The Court is not authorising sex-swap surgery. These critics have missed a crucial aspect of the judgment — and missed some subtleties in the decision. It is significant that the proposed treatment is a staged process that provides time for Alex to further explore the issue of gender identity. During this time, Alex will receive ongoing psychological and psychiatric support, which is an essential part of the proposed treatment authorised by the Court. Alex can elect to discontinue the treatment at any time.1 Is the treatment inappropriate?In response to the view that the treatment is inappropriate, it can be argued that treatment designed to reduce gender dysphoria is a “legitimate goal of intervention”, being treatment that reduces the degree of “social ostracism” and “psychiatric comorbidity”.19 For Alex, there is great benefit in being given permission to begin the first stage of treatment and there is great harm in not having his desire to live as a boy taken seriously. The benefits in commencing treatment are real, immediate and significant. Alex will gain immediate relief from distress, and his developing self-determination will be strengthened by having his preference acknowledged. Moreover, the first stage of treatment is completely reversible. Taking the pill on a continuing basis is not an unusual or bizarre treatment. Alex gains time, during which he will receive counselling and can further explore the issue of his gender identity, before the next stage of treatment goes ahead at age 16. Importantly, the decision allows for the possibility that Alex might change his mind. According to the Royal College of Psychiatrists report, a large element of management is “promoting the young person’s tolerance of uncertainty and resisting pressures for quick solutions”.6 Critics who assume that giving credibility to Alex’s preferences means he is set on an irreversible pathway ignore the role of the ongoing counselling support. Alex may decide not to proceed, but, if he does proceed, the counselling he will have received should assist him in having a clearer idea about his identity. The counselling will also help him to be better informed about the procedure and its implications. With this support, he is much more likely to be making an informed, autonomous decision. The harm of treating versus the harm of not treatingThe harms that may occur with the proposed treatment (eg, practical and social difficulties, victimisation, and the possibility of regret) are theoretical, while the harms of not proceeding with the proposed treatment are likely and substantial. According to the Royal College of Psychiatrists report, interventions that recognise and accept the problem of gender-identity disorders and remove the secrecy can bring considerable relief.6 In this regard, the Court’s decision, and the process that led to it, could be deemed therapeutic. The evidence presented tells of Alex’s depression and self-harming behaviour during the time when his desire to live as a boy was not taken seriously. Those who know him well are concerned that he may go back to the old behaviour if he is not permitted to commence the proposed treatment.1 The judge also expressed concern that, if the proposed treatment was not allowed to proceed, Alex’s “education and residential arrangements and his developmental socialisation would be jeopardised to his long term detriment”.1 It is worth noting that the proposed treatment is practised in The Netherlands and is recommended in the Standards of Care of the Harry Benjamin International Gender Dysphoria Association.20 While the application before the Court in this case did not include surgery, follow-up studies in The Netherlands on the postoperative success of transsexuals who began the treatment process in adolescence have noted improvement in the main treatment goal — that is, “diminution or resolution of gender dysphoria”.5 It was also found that these young people rated better in terms of psychological and social functioning than transsexuals who began treatment later on as adults. Postoperative regret occurs in some adults, but none of those who began the treatment process as adolescents experienced regret.5 These studies support the view that early intervention for those who continue on to pursue surgery can be justified by better outcomes. Competence to decideDifficult and complex issues also arise because of the questionable competence of a young person to make important decisions — especially decisions involving irreversible changes that could close off future options or be detrimental to long-term interests. We want to know whether the young person is competent and whether the decision is an autonomous one deserving respect (ie, a choice that is freely made “in accordance with a self-chosen plan”).21 The main values at stake in competence determinations for children and young people are wellbeing and autonomy (or, more aptly, their developing autonomy). Determining competence in young people involves trying to balance “protecting their wellbeing from the harmful consequences of their choices when their decision-making capacities are defective” with “respecting their interest in deciding for themselves when they are able”.22 Autonomy and making autonomous decisions requires stable values and a conception of the good, but instability is a feature of the values of children and young people. Young people “may give inadequate weight to the effects of decisions on their future interests, and also fail to anticipate future changes” in the things that are important to them.22 It can be argued that this case is unique in the sense that we do not have to grapple with the difficult issues of whether Alex is competent to make the decision, whether his decision is an autonomous one, and whether treatment of the kind proposed is appropriate only if its purpose is to cure a disease or correct a malfunction. These issues are eclipsed by considerations of benefit and harm. In this case, it is an added bonus that the proposed treatment is “entirely consistent” with what Alex wants, and that what Alex wants also accords with what the expert evidence indicates is in Alex’s best interests.1 It adds to the overall benefit. The Court’s decision is not about giving in to the unstable preferences of an immature person. In this case, the ultimate determinant of Alex’s wellbeing is his developmental needs rather than his capacity for deciding or his preferences. Part VII of the Family Law Act requires the Court to regard the child’s best interests when making medical treatment decisions. Rather than seeing the proposed treatment as closing off future options, it can be viewed as fostering Alex’s development and opportunities. Alleviating distress and thoughts of suicide benefit Alex’s mental and emotional health. According to his aunt, since commencement of plans to help Alex in his desire to live as a boy he has been happier, with improved behaviour, and “seems to have some direction and some plan for the future”.1 This case suggests that there is a point at which a condition that causes distress becomes medically significant. ConclusionThis case demonstrates the importance of weighing the benefits and harms involved in authorising or not authorising treatment. It highlights the value in respecting the developing autonomy of a young person, even though considerations about self-determination may not be the ultimate determinant of what should be done. In relation to the public debate, I believe that critics need better arguments to denounce the appropriateness of the proposed treatment. Critics have failed to recognise the benefit to Alex of having his wish to live as a boy taken seriously. Finally, the benefit that comes from the relief of distress may make us wonder whether the goals of the intervention really matter.

Merle P Spriggs BA, MBioeth, PhD

Correction Re: “A financial case to enable state health jurisdictions to invest in tobacco control”, by Seham T Girgis and Jeanette E Ward in the 17 November 2003 issue of the Journal (Med J Aust 2003; 179: 539-542). Statistical errors occurred in this article as follows. In Box 1 (page 540): The aetiological fraction for “cardiac dysrhythmias” for men aged less than 65 years was incorrectly cited as 0.538. It should read 0.358. The correct value was used in calculations. ICD-9 codes for “premature rupture of membranes” were used in calculations as given by Ridolfo and Stevenson (Ref 23, page 83). These were incorrectly cited as “658.1–658.2, 761.1”, but should read “658.1, 658.2, 761.1”. The correct ICD codes were used in calculations. The aetiological fraction for “ischaemic heart disease, cardiac dysrhythmias and heart failure” conditions for women aged 65 years and over was incorrectly cited and incorrectly used in calculations as 0.027. It should read 0.059. In Box 2 (page 541): The aetiological fraction for “oesophageal cancer” for women was incorrectly used in calculations as 1.324. Using the correct aetiological fraction (0.324), as correctly cited in Box 1 (page 540), reduces the number of hospitalisations for cancer by 3% and 2% in NSW and SWS women, respectively. “Heart failure” conditions for NSW were incorrectly calculated. Using the correct value, the number of hospitalisations in the “other” category for NSW men is reduced by 356 hospitalisations. These errors do not introduce substantive changes in our findings. However, the following changes should be made to the text: In the Abstract (page 539), replace the third and fourth bullet points with: Tobacco was responsible for 43 350 hospitalisations in New South Wales in 1999–2000 alone, incurring $176 096 323 in hospital costs ($482 456 per day). If the equivalent of a specified percentage of expenditure as calculated for one year were “invested” in tobacco control in the next year, then commitments to a substantive suite of health promotion programs could be made. For example, using our formula, a contribution of 3% would secure an annual tobacco control budget of $5 282 890 in NSW. In the case studies (pages 540–541), replace the state example with the following text: State exampleAs calculated for the 1999–2000 financial year, tobacco directly contributed to an estimated 43 350 hospitalisations in NSW (Box 2) constituting 3.1% and 1.5% of all hospitalisations for men and women, respectively. Tobacco-attributed hospitalisations accounted for 295 960 hospital bed-days, representing 3.5% of all bed-days in NSW (total, 8 337 286 bed-days). As the average bed-day cost in NSW hospitals for that period was reported as $595 per day,25 tobacco-attributed hospitalisation cost $176 096 323 in that 1 year alone ($482 456 every day). In NSW, major contributors to tobacco-related hospitalisations for men included ischaemic heart disease (28%) and cancer (20%). For women, the major contributor to tobacco-related hospitalisations was chronic obstructive pulmonary disease (29%). Lung cancer contributed to 4027 (2961 men; 1067 women) hospital separations attributed to tobacco use. This represented 54% and 57% of the cancer-related hospitalisations attributed to tobacco use in men and women, respectively. A proportional levy of 3%, as would be typically imposed upon public-sector organisations as an annual productivity saving, would secure an annual budget of $5 282 890 for NSW. Five per cent would secure an annual budget of $8 804 816. The changes outlined here have been made to the html and pdf versions of the text published online.

Seham T Girgis MB BCh, MPH · Jeanette E Ward MHPEd, PhD, FAFPHM

Objective: To assess the attitudes of final-year medical students to digital rectal examination (DRE) and their experience of performing DRE during clinical training.Design: Questionnaire-based survey.Setting and participants: All students in the final year of medical school at the University of Melbourne in 2003.Outcome measures: Agreement with statements about attitude to DRE; number of DREs performed and abnormalities palpated; and ratings of frequency of supervision and perceived barriers to performing DRE.Results: 222 of 256 students (87%) responded. Almost all (97%) believed that DRE is an essential requirement for a medical practitioner, and 94% that they should have the skill before graduating, while 92% said they had been taught how to perform it. The median number of DREs performed was two, with 17% of students performing none. Sixty-three per cent had palpated a prostate, 24% a prostate cancer, 19% a rectal tumour, and 11% faecal constipation. Half the students (52%) felt they could give a reasonable or confident opinion based on their DRE findings. The most often cited reason for not performing DREs was the lack of a doctor to act as a supervisor.Conclusions: A concerted effort is needed from academics, supervising doctors and students to improve medical students’ proficiency in performing DRE and confidence about their findings.

Nathan Lawrentschuk MB BS · Damien M Bolton FRACS, MD, BA

The National Diabetes in Pregnancy Advisory Committee (NDIPAC) is a multidisciplinary committee established in November 2000 by the Commonwealth Department of Health and Aged Care as part of the National Diabetes Strategy. On behalf of the NDIPAC, we present the first Australian consensus statement (endorsed by the Committee in February 2004) on diabetes control for women with type 1 or type 2 diabetes who are preparing for pregnancy: Women planning pregnancy should aim to achieve a target HbA1c value of < 7% (where the upper limit of the normal range for people without diabetes is < 6%) (If the normal range for people without diabetes is specified otherwise, the target HbA1c level should be < 1% above the upper limit of normal.) The following important qualifying statements apply: Women with diabetes should aim to achieve the best control of diabetes possible in preparation for pregnancy. This should include achieving blood glucose levels as close to the normal range as possible, while avoiding hypoglycaemia. Decisions about the precise glucose level targets to be achieved should be made on an individual basis, with collaboration between the woman and her healthcare team. Women who are able to achieve better control of their diabetes than the target value indicated above (eg, an HbA1c level of 6%) should be encouraged to maintain these levels in preparation for pregnancy. Other aspects of care are also important in preparation for pregnancy. These include healthy eating, taking folic acid supplements, and detection and treatment of other diabetes-related complications. It is recommended that tighter control of blood glucose levels (eg, HbA1c < 6% or within the upper limit of the normal range) be targeted once pregnancy is achieved to minimise the risk of pregnancy complications and long-term metabolic consequences for the child. These recommendations were made after reviewing and discussing the available data (the references listed here are a selection of the data sources considered the most relevant).1-15 The recommendations have now been endorsed by the Australasian Diabetes in Pregnancy Society, the Australian Diabetes Society, the National Diabetes Strategy Group and the Royal Australasian College of General Practitioners. The NDIPAC suggests that the recommendations be used to determine action strategies for improving outcomes in pregnancies complicated by diabetes. For example, they could be applied in: designing appropriate enhanced primary-care guidelines and target HbA1c levels for women in their child-bearing years; flagging pathology results (specifically, the HbA1c value in women of child-bearing potential) for action by treating clinicians; ongoing monitoring of pre-pregnancy glycaemic control using the framework of the National Diabetes in Pregnancy Audit Program (for more information, see the Australasian Diabetes in Pregnancy Society website, www.adips.org).

on behalf of the National Diabetes in Pregnancy Advisory Committee

Setting You are a registrar with a new intern who has had little experience with arterial puncture for blood gas analysis. You show her how to do one, then suggest she’ll get practice when on call that night. She could even show the medical student how to do them, so he can help out. Junior doctors need to have the skills to competently perform a wide range of procedures, and inability to do so is an important stressor for a new doctor.1 Skills may range from carrying out practical tasks (intravenous cannulation), to examining patients (cranial nerve examination), to communicating well (breaking bad news). Teachers rated practical skills teaching 11th in a list of educational themes they felt they needed instruction on, whereas junior medical officers ranked it 5th, suggesting that we don’t teach as well as we think we do.2 How are skills learnt?Simulated patients, videos, manikins, computers and virtual reality technology are increasingly being used to ensure that trainees learn skills in a safe environment, receive feedback, and reach a certain level of competence before they use the skills on patients.3 The first trainee year is critical for learning many of these skills.4 Skills centres are playing an increasing role these days, but the challenge is to make sure that laboratory-learnt skills are safely implemented in the workplace. Abundant opportunities arise during work that learners are eager to be involved with. As practising clinicians, part of our teaching role is to decide whether junior staff can safely carry out procedures on patients under our care. Skills require more than performing tasks. They include: Knowledge (indications, contraindications, complications and their prevention); Skill (preparation, technique, dexterity); and Communication (consent, comfort and dignity of patients; realising when to get help). How are skills learned on the job? The “see one, do one, teach one” approach is limited, often failing to teach the skill properly or to check whether the trainee can perform the skill. A four-step approach to teaching skillsOne way of teaching skills, suggested by Rodney Peyton of the Royal College of Surgeons,5 uses four steps: Demonstration. Trainer demonstrates at normal speed, without commentary. Deconstruction. Trainer demonstrates while describing steps. Comprehension. Trainer demonstrates while learner describes steps. Performance. Learner demonstrates while learner describes steps. This four-step approach ensures that the teacher breaks the process into manageable steps, asks the learner to vocalise the steps, and provides repetition to reinforce the learning and correct mistakes. Session structureIn applying Peyton’s model, consider the structure of the session, as described in “Tips 3”:6 Set. Have you made assumptions about the learners’ basic knowledge (“You know that, don’t you?”). Consider their orientation: are they sitting beside you or opposite (mirror image)? are they left- or right-handed? can they see? Dialogue. Have you broken the procedure into clear steps? Is the task too large to learn at one sitting? Are you giving positive feedback (what they did well, what they could improve)? Have you corrected mistakes? Avoid talking too much — either giving too much detail (trying to cover too much in one sitting) or chatting about something else (worried they are bored). Closure. Can they do it? Do you need to explain how the procedure may differ under different circumstances? Application in practiceRarely are four patients lined up to allow you to take someone through the four steps one after the other. However, each step adds an important component. How can the model be adapted to reality? Step 1 should be demonstrated with a real patient. It is important to allow the learner to identify with a competent performance. Steps 2 and 3 can be done theoretically or with the equipment, away from the patient. Steps 1 and 2 can be repeated in a larger group (eg, with a video), then steps 3 and 4 can be done in small groups. Steps should be done in more than one sitting. Consider the way you currently teach a skill and think about what the four-step approach may add Practice makes perfectBy following the four-step approach, the trainee has shifted from being “consciously incompetent” (realising they can’t do it) to being “consciously competent” (being able to do it with great thought) (Box). Only with repeated practice will he or she be able to perform satisfactorily in a variety of situations. Stages in acquiring skills

Fiona R Lake MD, FRACP · Jeffrey M Hamdorf PhD, FRACS

Clinical record A 36-year-old man was found semiconscious in a park. He was carrying a syringe which was later found to contain high-purity amphetamine. He became combative, and was sedated and intubated on arrival at a hospital emergency department. Preliminary examination revealed proptosis of the left eye, which was surrounded by swelling and erythema, and a small conjunctival laceration on the nasal aspect. Pupillary light reflexes were normal. Examination revealed track marks in both cubital fossae suggesting intravenous drug use, but no other abnormalities. Non-contrast computed tomography (CT) of the brain revealed two minute areas of high density in the left frontal lobe, interpreted as evidence of early infection. CT of the orbits revealed left-sided swelling of the subcutaneous soft tissue, interpreted as preseptal cellulitis. A fracture of the left orbital roof was also noted adjacent to a superior orbital phlegmon (Box 1A). A lumbar puncture was performed, and, with a provisional diagnosis of preseptal cellulitis and meningitis, the patient was empirically treated with broad-spectrum intravenous antibiotics (vancomycin, ceftriaxone, gentamicin and metronidazole), while remaining intubated in the intensive care unit. However, as the cerebrospinal fluid appeared normal on microscopy and biochemical examination and showed no growth on culture, the initial diagnosis was questioned. Magnetic resonance imaging of the brain and orbits was performed the day after presentation. This showed a 5 cm tract extending obliquely from the roof of the left orbit into the white matter of the left frontal lobe, associated with a fracture of the orbital plate of the frontal bone (Box 1B). Inflammatory changes, presumed infective, were noted superiorly within the left orbit, resulting in proptosis. It was concluded that the patient had incurred a penetrating injury of the left orbit entering through the nasal conjunctiva and extending superiorly to the globe, through the orbital plate of the left frontal bone, and into the frontal lobe. Treatment with vancomycin, ceftriaxone and metronidazole was continued, and the patient was successfully extubated after 5 days. He was then able to recount jumping over a fence and landing on bushes, a branch of which penetrated his orbit. Re-examination revealed a marked decrease in the soft-tissue swelling around the left globe, but significant limitation of movement of the left eye in all directions (Box 2). These findings, along with the known intracranial penetration and the possibility of retained organic fragments, necessitated surgical exploration. A superior orbitotomy revealed an abscess containing tiny fragments of organic matter. This was washed out. The abscess was sterile on culture. The orbital tract was explored, and further small fragments of organic matter were retrieved. A left frontal craniotomy and repair of the roof of the left orbit were performed concurrently. Over the ensuing 10 days, the patient’s ocular movements improved to near full range, but he had intermittent temperature spikes. Multiple blood cultures showed no growth. Transthoracic echocardiography revealed a vegetation on the tricuspid valve. Intravenous antibiotics were continued for a further 6 weeks to treat presumed infective endocarditis. Although the patient developed no further symptoms, magnetic resonance imaging of the brain 11 days after the initial surgery revealed an elongated abscess in the frontal lobe, its inferior end abutting a small fragment of intracranial bone. The left frontal craniotomy was reopened, and the abscess drained. Culture of the abscess again showed no growth, and the patient required no further surgical intervention. Transorbital intracranial penetration by a wooden foreign body is unusual.1 The resilience of the sclera and ability of the globe to be displaced usually protect the eye from perforation.2 Metallic objects and glass fragments are the foreign bodies most often encountered in the orbit.3 Although computed tomography is excellent for identifying these high-density objects, it is much less sensitive for low-density organic objects.4 Magnetic resonance imaging is more sensitive for delineating the extent of orbital injury and is safe when non-magnetic foreign bodies, such as wood, are suspected.5 Because of its porous organic nature and frequent proximity to soil, wood is an ideal reservoir for bacteria and fungi and is likely to provoke inflammation. A narrow deep tract, such as occurred in our patient, is conducive to the proliferation of anaerobic bacteria.6 The most usual complications of an orbital foreign body are proptosis of the eye, development of a chronic fistula, orbital abscess or cellulitis, and damage to the extraocular muscles or optic nerve.7 Intracranial extension of the foreign body is associated with a 48% incidence of brain abscess and a 25% mortality rate.1,6 This case illustrates the possibility that a seemingly trivial lesion, such as a conjunctival laceration, can be associated with severe lesions in the orbital region. This case demonstrates the need to suspect intracranial penetration in orbital injuries, as intra- and extracranial complications often lead to prolonged hospital admission and carry a significant risk of mortality . Lessons from practice The diagnosis of transorbital intracranial penetration of a foreign body requires a high index of suspicion, as it can present with trivial findings on examination. Intracranial penetration carries significant morbidity and often leads to local and systemic complications. Early magnetic resonance imaging is recommended when there is a possibility of transorbital intracranial penetration. 1 Imaging in a patient with an orbital fracture A. Computed tomography showed a fracture of the roof of the left orbit (F), adjacent to a superior orbital phlegmon (P). B. Subsequent magnetic resonance imaging showed a 5 cm oblique tract extending from the fracture of the orbital plate of the left frontal bone into the white matter of the left frontal lobe. 2 Limitation of movement of the left eye The patient is attempting to look to his right.

Dana Robaei MB BS(Hon), MPH · Glen T Fernando MB BS(Hon) · Charmaine MacDonald MB BS · Michael G Branley FRACO, FRACS

Research funding for CAM is inadequate, resulting in too few good quality studies to support its use. Widespread use of CAM, as well as its media promotion, make this a vital public health issue, and the Australian government has a social and ethical obligation to respond by developing a research infrastructure (as has been done by the United Kingdom and United States governments). We propose a funding model that neither draws directly from the CAM industry nor from current health research budgets, yet would strengthen Australia’s international role in CAM research. Establishing and applying focused research methods in CAM is imperative for strengthening its evidence base and creating fresh options for safe and effective patient care.

Alan Bensoussan PhD, MSc · George T Lewith DM, FRCP

CAM research is leading to changes in the vitamin cabinet and the clinic Many Americans use one or more health promotion, illness prevention or healing practices that are considered as complementary and alternative medicine (CAM).1 In recognition of this, the United States Congress legislated in 1991 to establish the Office of Alternative Medicine to “investigate and evaluate promising unconventional medical practices”. In 1998, Congress expanded this mandate by enacting legislation that created the National Center for Complementary and Alternative Medicine (NCCAM), endowing it with the resources and authority to fund research, train researchers, and disseminate information to the public and healthcare professionals. A number of factors contributed to the creation of NCCAM. First was the popularity of unproven medical practices, with users of one or more CAM modalities tending to be women, people with higher education, those with an interest in the role of the mind in health, or those with some chronic illness.2 Second was an increasing recognition of the importance of traditional healing practices among an ethnically diverse American population. Third, in 1994, the US Congress passed legislation that permitted wide access to dietary supplements without confirmation of their composition, safety or efficacy, and a concomitant loosening of legal restraints on alternative practices such as chiropractic medicine and acupuncture. Setting priorities — science firstGiven the diversity of CAM approaches and questions about their safety and efficacy, setting research priorities for NCCAM is a significant challenge. The US$117.7 million allocated to NCCAM in 2004, while generous by most standards, permits only a limited sampling of possible CAM approaches. To develop its approach, NCCAM sought input from diverse communities of stakeholders. The resulting first strategic plan stressed investment in basic and clinical research, training, dissemination of findings, and integration of safe and effective practices.3 NCCAM made a commitment to aspire to the same rigorous standards that characterise National Institutes of Health (NIH) research in general, while its research priorities would focus on the most promising scientific opportunities. As NCCAM celebrates its fifth anniversary, it is possible to list its not inconsiderable achievements to date (see Box 1), and to reflect on some of the lessons learned for current and future directions. Investing in research centresTo create a sustainable research infrastructure, NCCAM funded a first generation of research centres spanning a range of health disorders and disciplines. Based on formal reviews, a second generation of more focused centres is being developed. Some of these are involved in elucidating mechanisms of action of CAM therapies. Others promote collaborations between CAM and conventional institutions. Still others represent new initiatives to forge scientific partnerships between investigators at US and foreign institutions. Botanical trials — overcoming obstaclesWhen NCCAM was created, it was assumed that existing literature on herbal supplements would be sufficient to justify and design major studies of their safety and efficacy. It quickly became apparent that many botanical preparations are not standardised, and may be contaminated with heavy metals or drugs,4 precluding the conduct of meaningful and ethical studies. As a result, NCCAM is now working with academic and industrial partners to identify more optimal research-grade materials, and requires evidence of product quality for all its sponsored research. These approaches raise the quality of the studies, but consume time and resources. Phase III clinical trials — balancing pressure for progressThe results of NCCAM’s very first large clinical trial dictated a more deliberate and phased approach for future studies, even when high quality products are available. The three-arm randomised controlled trial failed to show that Hypericum perforatum (St John’s wort) ameliorates major depression.5 Advocates for the product faulted the study for having addressed too serious a form of depression. While the target population, the product, its dose, and endpoints had been thoroughly discussed, it was ultimately clear that more preliminary research and consensus development was needed to determine the optimal design of other large trials. Such efforts are being made now in trials of Ginkgo biloba for cognitive decline in the elderly, and glucosamine for osteoarthritis. Each of these, and other ongoing trials (Box 2), are being conducted with input from relevant communities of patients, practitioners and scientists, and cofunded by other NIH institutes. Brain–mind–body medicine — an emerging scienceThe capacity of the brain and mind to affect health is a CAM domain that is receiving more attention at NCCAM. Surveys indicate that about one in five adults use at least one mind–body therapy.6 Functional neuroimaging provides powerful new tools to identify changes in brain structures involved in generating emotional responses, interaction of distress and pain, and response to treatment. With this and other new laboratory and ambulatory methods, NCCAM is funding investigators to identify pathways of influence, and to test interventions, such as meditation in preventing illness, slowing disease progression and promoting well-being. Planning for the futureLessons learned at NCCAM forecast a future with a greater emphasis on preclinical and early-phase clinical studies that are designed to elucidate mechanisms, identify optimal dosing and schedules, and select appropriate target populations and control conditions before launching clinical trials. Clinical studies at all levels are increasingly being conducted as collaborative efforts between funded investigators and NCCAM staff, who provide technical guidance, from sophisticated design and statistical consultation, to advice on recruitment and retention. Research on natural products is being conducted within a framework in which NCCAM either provides well-characterised and standardised clinical trial materials for investigators to use, or tests products being used by investigators to assure characterisation and standardisation. Finally, NCCAM is taking full advantage of new technologies, from genomics to brain imaging, and applying them to new areas, such as the capacity of the mind to affect health, in its multidisciplinary research. While NCCAM first built a domestic scientific constituency, it seeks to engender and strengthen relationships with other countries that have both established research in conventional medicine, and a tradition that is rich in indigenous practices. We invite scientific leaders in these countries to join the global CAM research effort. 1 Activities of the National Center for Complementary and Alternative Medicine in its first 5 years It built a centre responsive to its mission and integrated into the other institutes at the United States National Institutes of Health It funded over 780 projects at 123 institutions, resulting in over 700 scientific publications It awarded more than 100 individual doctoral and postdoctoral training and career awards It enrolled nearly 40 000 participants in clinical protocols It received over 1.5 million visitors to the website <www.nccam.nih.gov> each year who search for information about CAM, clinical trials, and research opportunities It developed a database known as “CAM on PubMED” that lists nearly 400 000 articles on CAM-related subjects published in 45 languages from 70 countries It informed public policy, patient choice, and clinical practice through outreach activities, including public town meetings, public media, and scientific and professional conferences 2 Status of National Center for Complementary and Alternative Medicine Phase III Clinical Trials Complementary and alternative medicine modality Target disease Sample size Status National Institutes of Health Partner Acupuncture Osteoarthritis 570 Trial complete; analysis underway NIAMS Glucosamine/chondroitin Osteoarthritis 1 588 Enrolment complete; ongoing NIAMS Ginkgo biloba Dementia 3 073 Enrolment complete; ongoing NINDS, NIA, NIMH Shark cartilage Lung cancer 756 Patients enrolling; ongoing NCI Vitamin E Prostate cancer 32 400 Enrolment complete; ongoing NCI St John’s wort Minor depression 300 Patients enrolling; ongoing NIMH, ODS EDTA chelation therapy Coronary artery disease 2 372 Patients enrolling; ongoing NHLBI Saw palmetto Benign prostatic hyperplasia 2 860 Final protocol under development NIDDK, ODS NIAMS = National Institute of Arthritis and Musculoskeletal and Skin Diseases; NINDS = National Institute of Neurological Disorders and Stroke; NIA = National Institute on Aging; NIMH = National Institute of Mental Health; NCI = National Cancer Institute; ODS = Office of Dietary Supplements; NHLBI = National Heart, Lung, and Blood Institute; NIDDK = National Institute of Diabetes and Digestive and Kidney Diseases.

Margaret A Chesney PhD · Stephen E Straus MD

Rosalie C Viney,* Madeleine T King,† Elizabeth J Savage,‡ Jane P Hall§ * Senior Lecturer, † Lecturer, ‡ Senior Lecturer, § Professor, Centre for Health Economics Research and Evaluation, University of Technology Sydney, PO Box 123, Broadway, NSW 2007. Rosalie.vineyATchere.uts.edu.au To the Editor: Segal et al propose a new method — “transfer to utility” (TTU) — to convert clinical and quality-of-life (QOL) trial-based outcome measures to a common metric — quality-adjusted life-years (QALYs) — to compare the cost-effectiveness of different interventions.1 TTU uses regression to map clinical and QOL instruments to a “utility-equivalent scale” that aims to measure strength of preference for health outcomes. In their example, several instruments were administered to osteoarthritis patients. Australian Assessment of Quality of Life (AQoL) scores were regressed on SF-36 subscale scores and QALYs were generated from published SF-36 results by means of a conversion algorithm based on these parameter estimates. The approach is novel, but we question its validity. Utility and health-related quality of life (HRQOL) are fundamentally different concepts. HRQOL is a standardised multi-dimensional, ordinal measure of the individual’s perception of how disease and treatment affect physical, social and emotional functioning. Measuring utility requires a critical next step: capturing strength of preference for outcomes in a unidimensional interval scale. HRQOL and utility scales have very different interpretations. Any appearance of similarity is superficial. The algebra of scale conversion is easy, but conceptually problematic. TTU involves a complex trail of estimation and prediction. Ordinal SF-36 subscale scores are used as arguments in regression, imposing interval properties. Statistically valid interpretation of the resulting parameters requires dummy coding. The dependent variable is the AQoL score generated by applying the AQoL algorithm, developed in previous research using a different population2 to respondents’ surveys. The new algorithm from the TTU regression parameters is used to convert published trial-based average SF-36 subscale scores to AQoL scores. Misspecification errors are built into the predicted AQoL scores. Information about variability in outcomes and preferences in intermediate measures, and hence uncertainty around point estimates of predicted AQoL scores, is suppressed. How plausible are these results? Segal et al report an estimated “utility gain” 12 months after hip surgery of 0.304 (from 0.464 before surgery to 0.767 at 12 months).1 The interpretation is that an average patient undergoing hip surgery for osteoarthritis would be willing to forgo about 40% of their remaining life span for the quality-of-life improvement the surgery would provide. Apparently, sophisticated quantitative approaches cannot add information about factors not measured in trials. The validity of the approach stands or falls on appropriate statistical methods, data quality and interpretable results. TTU potentially introduces bias, suppresses information relevant to decision-making and may lead decision-makers to place undue trust in point estimates based on heroic assumptions.

Rosalie C Viney · Madeleine T King · Elizabeth J Savage · Jane P Hall

Leonie Segal,* Richard H Osborne,† Susan E Day‡ * Deputy Director, ‡ Research Fellow, Health Economics Unit, Monash University, PO Box 477, West Heidelberg, Melbourne, VIC 3081. † Senior Lecturer, Centre for Rheumatic Diseases, University of Melbourne, Melbourne, VIC. Leonie. SegalATbuseco.monash.edu.au In reply: The “transfer to utility” TTU technique was devised to compare disparate interventions, using published clinical trial literature, where utility data are not reported. While collection of utility data in clinical trials would be preferable, until this occurs routinely a means to translate reported quality-of-life scores into utility scores is highly useful. Other groups are also grappling with this.1 In developing the TTU weights, various sophisticated statistical techniques were explored. However, added complexity did not improve the estimates. Contrary to the suggestion by Viney and colleagues, the TTU estimates are highly plausible and were vetted by our reference panel of clinical experts. Taking the example Viney and colleagues cite, a 0.304 increase in utility score for hip replacement indicates a patient would, on average, be willing to forgo 30.4% of remaining life-years to obtain the benefits of surgery — not 40% as incorrectly stated by Viney et al. This is consistent with the large increase in well-being observed following hip replacement (in the seminal trial, SF-36 mean scores increased from 26.9 to 66.6 for physical function, 14.6 to 58.7 for role physical, and 32.9 to 72.8 for bodily pain). Whether the TTU introduces bias (a characteristic of other summative approaches to estimating health, such as the popular DALYs) is a matter for future research. Undoubtedly, all population-wide approaches suppress specific information, but the purpose of the priority-setting model supported by the TTU is not to provide information on individuals, but to compare management options to give clinicians and policymakers another way of understanding the comparative performance of disparate interventions.

Leonie Segal · Richard H Osborne · Susan E Day

Chris G Fenn Medical Consultant, Pfizer Australia Pty Ltd, 38–42 Wharf Road, West Ryde, NSW 2114. chris.fennATpfizer.com To the Editor: At Pfizer, we are very concerned about major conclusions drawn with regard to cost-effectiveness of COX-2- specific inhibitors (CSI) in the article by Segal and colleagues;1 these conclusions are based on an entirely inadequate and inappropriate database. The CSI cost-effectiveness analysis is based on two publications described by Segal et al as “seminal”,2,3 and on a British Medical Journal editorial described as “a report by the US FDA [United States Food and Drug Administration]”.4 The first of the two “seminal” publications was a pivotal study for registration purposes;2 the second was neither pivotal nor “seminal”.3 The purported “report by the FDA” presents the authors’ opinion of a single study5 which does not reflect the overall body of gastrointestinal (GI) safety data for either CSI or non-steroidal anti-inflammatory drugs. The issues with this study and the inaccuracies in the editorial have been reported.6 Segal et al1 have apparently ignored at least 20 other publications (references available on request) comparing the safety and efficacy of celecoxib with NSAIDs; we would consider these relevant to any valid analysis of cost-effectiveness. There are probably a similar number of relevant publications for the second CSI, rofecoxib, which should also be considered if an analysis of the CSI class is to be rigorous. The body of evidence (previously summarised7) shows that CSIs are associated with a 50% or lower incidence of serious GI complications than non-specific NSAIDs, which results in lower mortality. Any cost-effectiveness analysis that ignores this GI safety advantage of CSIs over NSAIDs is incomplete. Therefore, the conclusions by Segal et al that “Non-specific NSAIDs and COX-2 NSAIDs were found to perform similarly in terms of outcomes and side effects . . .” and “ . . . In most scenarios, COX-2 NSAIDs are dominated by non-specific NSAIDs”1 are not true reflections of either the trial data nor real-world clinical practice, and may mislead the medical community as to the relative safety of these agents. It is important to note that the full body of celecoxib data has been submitted by Pfizer as a cost-effectiveness analysis to the Pharmaceutical Benefits Advisory Committee (PBAC). Contrary to the conclusions of Segal et al, in every scenario in the PBAC submission celecoxib was more cost-effective than non-specific NSAIDs. Celecoxib is currently listed on the Pharmaceutical Benefits Scheme and this indicates that it was considered cost-effective. An abstract has been published regarding the cost-effectiveness of celecoxib in the Australian setting.8 We consider that every statement made in the article by Segal et al with regard to the cost-effectiveness of COX-2-specific inhibitors1 is inaccurate and misleading, as it is not based on the available evidence. We request a retraction statement from the authors.

Chris G Fenn

Leonie Segal,* Richard H Osborne,† Susan E Day‡ * Deputy Director, ‡ Research Fellow, Health Economics Unit, Monash University, PO Box 477, West Heidelberg, Melbourne, VIC 3081. † Senior Lecturer, Centre for Rheumatic Diseases, University of Melbourne, Melbourne, VIC. Leonie. SegalATbuseco.monash.edu.au In reply: Our economic analysis of COX-2-specific inhibitors (CSIs) was part of a research program on priority setting. The application to osteoarthritis (OA) involved cost–utility analyses of 19 interventions (written up in a 195-page research report1), and was subject to peer review by an advisory panel including senior clinicians. The research drew on over 200 references, 23 on CSI, but a limit of 50 references for articles in the Medical Journal of Australia meant that full referencing was not possible. Evidence of efficacy in OA and adverse events (gastrointestinal and cardiac) are incorporated in our QALY estimates, the latter based primarily on the seminal CLASS trial (Celecoxib Long-term Arthritis Safety Study), and the United States Federal Drug Administration (FDA) analysis2-4 of this trial (summarised previously5). The FDA report concludes that for the primary endpoint specified in the study protocol — clinically significant upper gastrointestinal event (CSUGIE) — for the entire study period there was no significant difference in adverse events between the celecoxib arm and the combined diclofenac/ibuprofen arms (P = 0.45).2 Using the broader definition — combined CSUGIE and gastroduodenal ulcer (CSUGIE/GUD) — a significant difference is reported between combined non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and celecoxib (P = 0.040), but not with diclofenac (P = 0.295).2 The FDA concluded that “celecoxib was not able to demonstrate it was statistically superior to diclofenac in terms of the clinically important UGI [upper gastrointestinal] endpoints and conditions defined in this study. The same is not true when comparisons are made to ibuprofen.”2 The dominance of non-specific NSAIDs reflects celecoxib priced at $32.13/month (for 200 mg/day) and diclofenac at $13.42/month (for 75 mg/day)6 and evidence of equivalence in management of OA and GI side effect profile. We agree this does not support a conclusion about class dominance. All NSAIDs and all CSIs are not the same. Celecoxib is listed on the Pharmaceutical Benefits Schedule, but, as submissions by companies to the Pharmaceutical Benefits Advisory Committee (PBAC) are confidential, the research team may not have had access to all relevant evidence. We would welcome access to such information from which to prepare revised estimates. Placing all submissions to the PBAC in the public domain, as now occurs with reports of the PBAC, would allow a more informed public debate on these matters and would be most welcome.

Leonie Segal · Richard H Osborne · Susan E Day

Tarney J Spencer,* Ben Clark† * Ophthalmology Registrar, † Ophthalmologist, Geelong Hospital, Ryrie St, Geelong, VIC 3228. drtarnAThotmail.com To the Editor: We are concerned about the recent number of patients presenting to our hospital after accidentally applying superglue to their eyes. Of the four cases in February and March 2004, two arose from patients mistaking cosmetic nail adhesive for their regular ocular lubricant, and applying it to the inferior ocular fornices, creating a tarsorrhaphy. Superglues are cyanoacrylate derivatives. Those used domestically are lower-alkyl derivatives than those designed for medical use and have higher tissue toxicity. The two patients who mistook nail glue for ocular lubricant both required surgical separation of the upper and lower eyelids, and both had significant corneal abrasions, periocular dermatitis and temporary loss of lashes as a result of the reparative surgery. Both were treated with chloromycetin ointment until the abrasions had healed. We examined the bottles containing the nail adhesives. They were remarkably similar to many ocular lubricant bottles, with no significant difference in size, colour or feel (Box). As both products are often kept together in a cosmetics area of the bathroom, accidental ocular application can occur. Similar cases have been reported in other countries over the past 20 years.1-3 The risk of accidental ocular (or potentially aural) application could be reduced by changes to bottles containing superglue, including: childproof cap to prevent conventional opening of the bottle; colour coding of the bottles; different bottle shape; and distinctive odour and/or colouring of the glue. Superglue and eye lubricant bottles Examples of bottles of synthetic nail adhesive (two on left) and eye lubricant (two on right), showing similar appearance and feel.

Tarney J Spencer · Ben Clark

Jeremy J N Oats,* H David McIntyre† (on behalf of the Australasian Diabetes in Pregnancy Society, in conjunction with the Women’s Health Committee of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists) * Clinical Director, Department of Women’s Services, Royal Women’s Hospital, Carlton, VIC; † Director, Department of Endocrinology, Mater Health Services, South Brisbane, QLD. jeremy.oatsATrwh.org.au To the Editor: Consensus guidelines for the management of gestational diabetes mellitus (GDM) were prepared by the Australasian Diabetes in Pregnancy Society in 1997–1998 and subsequently published in the Journal.1 Since that time, there have been two minor revisions to these guidelines. The first, in relation to the recommended frequency of follow-up testing of women identified as having GDM, was detailed in a letter to the Editor in 2002.2 The second concerns the timing of delivery of women with GDM. At the request of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the original recommendation that “continuation of the pregnancy in uncomplicated GDM to 10 days beyond term is acceptable provided that indications from fetal monitoring are reassuring” has been modified by replacing “10 days beyond term” with “full term” to bring this into line with current practice. The initial guidelines were arrived at by consensus of Australasian practitioners involved in the care of women with GDM. The Australasian Diabetes in Pregnancy Society recognised, both at the time and subsequently, that the level of evidence available to guide clinical decision-making fell well short of that necessary for a definitive statement on the timing of delivery. It is noteworthy that no international consensus exists concerning the optimal timing of delivery in pregnancies complicated by GDM. The American Diabetes Association, in its Clinical Practice Guidelines, recommends delivery “during the 38th week . . . unless obstetric considerations dictate otherwise”.3 The European Association of Perinatal Medicine does not make a recommendation, instead stating that “the optimal time of delivery and need to induce labour are still controversial.”4 There is currently a paucity of quality evidence on which to confidently base recommendations. We hope that current studies, such as the Australian Carbohydrate Intolerance in Pregnancy Study and the Hyperglycemia and Adverse Pregnancy Outcome Study,5 will provide this evidence.

Jeremy J N Oats · H David McIntyre

A Rod MacQueen Clinical Director, Drug and Alcohol Services, Mid Western Area Health Service, Bloomfield Hospital, Forest Road, Orange, NSW 2800 rod.macqueenATmwahs.nsw.gov.au To the Editor: The article by Martyres et al on drug-seeking behaviour by young heroin users,1 leading to the deaths of 202 people over 5 years, leads to an inescapable conclusion. Too often, the medical profession is part of the problem rather than the solution, and as a result young people die. Here is an issue where the admonition primum non nocere should be foremost in our practice. After working with drug users and prescribing methadone for 22 years in a variety of settings, my experience is that drug users use drugs! Whether it is logical, safe or appropriate, or not, this group seeks drugs to modify or modulate their state of being. They often have serious medical and mental health issues, but have sadly decided on their preferred treatment without much knowledge of the diagnosis or of alternative interventions. They are often very skilled in obtaining drugs. So, we must perform our role equally well. Doctors are not drug dealers. Our duty is not to promote or support intoxication, or even relaxed happiness if that increases the risk of misadventure. It is to promote and support health. It is difficult to see how a prescription for 50 benzodiazepines to a young person (or even an older person) can ever be construed as healthcare. To do it again next day, next week, on and on, is almost unbelievable, yet the data indicate that is exactly what is happening.1 Even publicans have rules prohibiting serving intoxicated patrons. That one was “offering the customer what he asked for”, a common excuse for this sort of prescribing practice, would not be a suitable defence in the Coroner’s Court if insulin, digitalis, or even vitamin A, had been prescribed on request. But appeals to good practice and commonsense, along with current regulatory strategies, are apparently not sufficient to protect this vulnerable group. Kamien points out that data from the HIC could be used to provide immediate information to doctors about whether a patient is a “doctor shopper”.2 The data are already collected and could easily be made available if the will existed. Potential prescribers could at least gain accurate and timely information on which to base their decisions. There would be less excuse for “convenience store” prescribing, and more chance of ethical behaviour. At present these data remain largely useless in preventing avoidable deaths. But, surely, learning nothing from the deaths of 202 young Australians is not an option?

A Rod MacQueen

John M Hart General practitioner, Swan Medical Centre, 280 Great Eastern Highway, Midland, WA 6056 swanmedATiinet.net.au To the Editor: I write to share my concerns about the “doctor shoppers” in our community.1 The large medical group in which I practice has long been tormented by the demands of a constant stream of drug addicts, and I feel that we have now lost a very useful tool for dealing with these patients. I refer to the loss of access to the “Doctor Shopping Hotline”. This has resulted in increased aggravation for both staff and doctors. The problem is compounded by our practice being open at weekends and public holidays, when these patients arrive with the familiar story of not being able to get their benzodiazepines and opiates because their own doctors are not available. The Health Insurance Commission recently notified me about a patient who had attended our surgery, and many others, during a 3-month period last year. During this time, he saw more than 30 doctors and was prescribed more than 300 Pharmaceutical Benefits Scheme (PBS) items (6000 benzodiazepines and more than 2000 opiates [Panadeine Forte]). I strongly feel that the hotline should be reinstated — for the benefit of the doctors and the patients, and to help reduce a totally unwarranted drain on the PBS.

John M Hart

Jeff Whalan Managing Director, Health Insurance Commission, PO Box 1001, Tuggeranong, ACT 2901 medicare.enqAThic.gov.au In reply: I note the concerns expressed by Hart in relation to the discontinuation of the Doctor Shopping Hotline, and his call for the reinstatement of such a service. The Doctor Shopping Project, which was funded to the end of June 2002, focused on a limited selection of nervous system medications. It has been replaced by the Prescription Shopping Project, which is much broader in scope, as it encompasses all medicines on the Pharmaceutical Benefits Scheme (PBS). The new project aims to reduce the number of patients obtaining PBS medicines in excess of therapeutic need, and provides the opportunity for more informed prescribing across all categories of PBS medicine. The Health Insurance Commission (HIC) recognises the value of an information service for medical practitioners under the Prescription Shopping Project. An independent researcher has been engaged to explore the reactions and attitudes of medical practitioners and consumers to implementing such an information service. The research also aims to gain insight into medical practitioners’ intentions of using such a service, and their expectations of the scope and delivery of the service. Findings were presented to the HIC in early July 2004. The HIC will now convene a forum of relevant peak bodies to consider the scope and delivery of an information service in light of the findings. The HIC looks forward to working with the profession to establish an information service for medical practitioners under the Prescription Shopping Project.

Jeff Whalan

T C K Brown Former Director of Anaesthesia, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052. tckbrownATnetspace.net.au To the Editor: The epidemic of recreational use of γ-hydroxybutyrate (GHB; also known as γ-OH) is a cause for concern, as it is a basal anaesthetic agent (ie, it renders the patient unconscious, with analgesic supplementation required for surgery). It is not surprising that people taking too much of it are becoming unconscious.1 GHB was introduced in France as a basal anaesthetic agent by Laborit about 1960. It has a slow onset of action (up to 10 minutes when given intravenously, thought to be due to conversion to an active metabolite, γ-butyrolactone).2 It causes bradycardia, sometimes requiring atropine administration to maintain cardiac output, and raises blood pressure. Respiration is slow and deep, so that alveolar ventilation is not reduced. Trials of GHB as an anaesthetic were conducted in Melbourne by Dr William Cole and myself in the late 1960s,3-5 and it was used for microlaryngeal surgery for several years. Its major problems were prolonged sleep (1–3 hours after 40–100 mg/kg in children) and a high incidence of postoperative vomiting, adding the danger of aspiration in unconscious patients. GHB was also tried as an anaesthetic in Dunedin, New Zealand, where it was found that the sleep time could be reduced by intravenous administration of physostigmine.6 The fact that this drug is a basal anaesthetic needs to be more widely publicised.

T C K Brown

Geoffrey M Forbes,*† Matthew J Zimmerman, † Brendan J Collins,† John T Edwards† * Head, † Gastroenterologist, Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, WA. geoff.forbesAThealth.wa.gov.au To the Editor: The editorial by Viiala and Olynyk on screening flexible sigmoidoscopy (FS)1 is a welcome reminder that there are alternative colorectal neoplasia (CRN) screening strategies to the Australian National Health and Medical Research Council’s preferred option of annual faecal occult blood testing. The availability of tests for CRN screening raises the issue of whether screening tests should be dictated by government or professional bodies, or requested by the consumer. FS and colonoscopy remain potential alternatives to faecal occult blood testing in Australia, as reflected by US screening guidelines2 and recent local data.1,3 However, it is unreasonable for Viiala and Olynyk to compare the risks of screening FS (generally diagnostic only) in average-risk subjects (perforation rate, 1/50 000) with the risks of colonoscopy (both diagnostic and therapeutic) in Western Australian tertiary hospital outpatients with symptoms or other risk factors for CRN (perforation rate 1/1000). Firstly, it is important to recognise that the perforation risk associated with screening FS comes not just from the diagnostic screening test (1/50 000), but also from follow-up colonoscopy and subsequent polypectomy in patients with distal adenomas seen on FS. Secondly, in the WA tertiary hospital cohort,4 the estimated perforation rate for diagnostic colonoscopy is about 1/2800 (and about 1/420 for colonoscopy accompanied by polypectomy). Asymptomatic subjects having screening colonoscopy are likely to have a lower risk than patients with symptoms or other significant comorbidities having investigative colonoscopy. Recent data from colonoscopic screening programs (which include subjects having polypectomy) have shown an overall perforation rate of less than 1/3000.5 Medical practitioners arranging colonoscopy, and people having this procedure, should be informed about the risks involved and, importantly, be aware that these risks are likely to vary according to the setting in which colonoscopy is performed.

Geoffrey M Forbes · Matthew J Zimmerman · Brendan J Collins · John T Edwards

Paul Prociv Honorary Research Consultant, School of Molecular and Microbial Sciences, University of Queensland, Brisbane, QLD 4072. p.procivATmailbox.uq.edu.au To the Editor: In their brief review of water and public health, Leder et al1 uncritically attributed the Palm Island “epidemic” of 19792 to algal toxicity, commenting that it was the only recorded manifestation of this phenomenon in Australia. The original report described a hepatitis-like illness (associated in many with dehydration and bloody diarrhoea) in 138 children and 10 adults of Aboriginal and Torres Strait Islander descent living on Great Palm Island, northeast of Townsville, Queensland.2 No causative agent was actually identified. My investigation in the early 1980s of Toxocara pteropodis, a parasite of flying foxes, excluded it as a likely aetiological agent in the Palm Island outbreak, and compelled a critical reanalysis of other possibilities, which led me to conclude that subacute copper toxicity was the most plausible explanation. My rationale was published as a hypothesis.3 Sadly, discretion (to protect local technicians) compelled me to withhold critical information that explained how the community had been inadvertently exposed to excessive levels of copper in its water supply. Now that water management is becoming a major societal concern and algal blooms seem to be increasing in frequency, the issue needs to be resolved — and sufficient time may have elapsed for details to be revealed without impugning individuals. In 1985, having concluded that copper poisoning was the most likely explanation, I contacted the environmental health personnel who had overseen the mixing of algicide into the Palm Island water supply in 1979. They were aware that the actual volume of water to be treated had probably been grossly overestimated, because Solomon Dam’s water level was very low at the time. This meant that an excessive dose of copper sulfate was added to the dam, but it was assumed that this would be “erring on the safe side”. Further, the copper sulfate was not distributed uniformly through the water in the dam: a local resident with a dinghy had been contracted and instructed to spread the bags of copper salt around the dam, but had instead dumped it all at one place — immediately over the outlet pipe which carried the island’s drinking water. This would readily explain how the community encountered a sustained pulse of high copper levels in its tap water. While chronic copper poisoning can lead to infantile hepatic cirrhosis,4 acute gastrointestinal symptoms (as manifested during the Palm Island episode) are also well documented.5,6 In the absence of laboratory confirmation of copper toxicity, the cause of the “Palm Island mystery disease” must remain speculative. However, in any future similar outbreaks, copper poisoning should be excluded before attributing the cause to algal toxicity.

Paul Prociv

Cardiovascular disease is the leading cause of morbidity and mortality in Australia. It is therefore important that all medical practitioners are familiar with the well documented risk factors for cardiovascular disease, as well as the outcome benefits of pharmacological and other interventions. The large and ever-increasing body of clinical evidence, the range of patient groups at risk and the plethora of recommended interventions all make it increasingly difficult for busy doctors to adopt an integrated approach to prevention of vascular events. While absolute risk calculators, such as the Framingham Heart Study Prediction Score Sheets (www.nhlbi.nih.gov/about/framingham/riskabs.htm) or the New Zealand Cardiovascular Risk Factor Calculator (www.racp.edu.au/bp/resources/EBM_cardio.pdf), enable doctors to assign overall risk, guidelines for management are usually focused on single interventions. Moreover, the continual emergence of new data on vascular risk management redefines risk categories and approaches to risk management. Prevention of cardiovascular disease: an evidence-based clinical aid was developed by a multidisciplinary group of physicians to address this issue and was first published by the MJA in July 2003. We have revised and updated our evaluation of current best practice based on a rigorous analysis of available published evidence to March 2004, and formulated a concise and up-to-date guide for the prevention of cardiovascular disease. This consensus of opinions is summarised in this document (see Clinical aid, page F12) and provided as a single-page chart for use in clinical practice as a desktop reference. Patients were classified as being either at high or low risk of cardiovascular events (Box 1). It is widely considered that high-risk patients are those with clinically evident vascular disease, renal disease, diabetes or other risk factors conferring an annual risk of a future event of 2%–3% or greater. Risk can be calculated using an absolute risk-factor calculator (see above). The major interventions considered were: lifestyle changes; cessation of smoking; and treatment of hypertension and dyslipidaemia. Where new indications for treatment have been demonstrated in particular circumstances for a single product, this product is shown; otherwise, the class of agents is presented. We considered the results of recent trials that will potentially have a major impact on the management of high-risk patients. Such trials include the HOPE study,1 the PROGRESS study2 and the Heart Protection Study.3 Furthermore, the recognition that proteinuria imparts substantial risk warranted the inclusion of specific advice for the population with this risk factor. Although the importance of homocysteine, Lp(a) and fibrinogen as cardiovascular risk factors was recognised, the infrequent measurement of these parameters in usual practice, together with the lack of proven interventions, justifies their omission from this review. We anticipate further updates and revisions to the aid to maintain its currency in the context of a rapidly expanding cardiovascular evidence base. The management recommendations of this “living” document will continually evolve as new evidence is published. It should be noted that this clinical aid applies to the long-term management of cardiovascular risk in general practice or community-based physicians’ practice. It does not cover the medical management of acute coronary syndromes or heart failure. Glossary of abbreviations ACE inhibitor – angiotensin-converting enzyme inhibitor AIIRA – angiotensin II receptor antagonist AMI – acute myocardial infarction CCF – congestive cardiac failure CHD – coronary heart disease HDL cholesterol – high-density lipoprotein cholesterol LDL cholesterol – low-density lipoprotein cholesterol RCT – randomised controlled trial TIA – transient ischaemic attack Recommendations for all patientsHealthy lifestyleAdvice concerning the benefits of smoking cessation, physical activity and healthy dietary choices should be given at a population and individual level. These measures are considered as first-line in any management decisions. a) Cessation of smokingThere is extensive evidence that smoking is strongly related to mortality, largely because of an increased risk of CHD and stroke.4 Furthermore, smoking cessation has been shown to decrease this risk in patients with and without established CHD.5 In patients with peripheral vascular disease or stroke, smoking cessation is associated with improved exercise tolerance and survival, and decreased rates of limb amputation and recurrent stroke.5 b) ExerciseWhile there is limited evidence from RCTs of the value of exercise in primary prevention of cardiovascular disease, there is strong observational evidence that moderate, regular physical activity reduces the risk of both CHD6 and stroke,7 and that the risk is increased in people with a sedentary lifestyle.8 For secondary prevention after AMI, two meta-analyses of exercise-based rehabilitation in up to 14 RCTs have shown reductions in mortality of between 20% and 25% (absolute risk reduction [ARR], 3.1%) at 3-year follow-up, although many of the trials allowed other risk-factor intervention as well.9,10 While these data must be interpreted with caution, prescribing a moderate degree of regular physical exercise is consistent with published evidence. c) DietCohort studies have shown that eating fruit and vegetables reduces the risk of heart attack and stroke.11 One RCT showed that a Mediterranean diet decreased mortality by 30% at 27 months after AMI (ARR, 4.0%).12 In addition, a modest intake of fish (as little as 35 g daily) appears to decrease the relative risk of AMI.13 Following general advice to decrease the intake of saturated fats and cholesterol and increase the intake of polyunsaturated fats favourably affects serum lipid levels and decreases the likelihood of CHD.14 Finally, weight maintenance education should be part of routine advice for the general population, but is particularly important in patients at increased risk of cardiovascular events. d) StressRecently, an Expert Working Group of the National Heart Foundation of Australia undertook a review of the evidence relating to major psychosocial risk factors to assess whether these influenced the development of CHD and acute coronary events.15 They concluded that there was “no strong or consistent evidence for a causal association between chronic life events, work-related stressors (job control, demands and strain), type A behaviour patterns, hostility, anxiety disorders or panic attacks and CHD”.15 However, there was strong and consistent evidence of an independent and causal association between depression, social isolation and the prognosis of CHD and, importantly, the impact of these was of a similar order to conventional risk factors such as smoking.15 It is therefore crucial that these psychosocial factors are considered during individual CHD risk assessments. Recommendations for patients with established vascular disease1. Normotensive patients with a history of cardiovascular diseaseThe HOPE,1 PROGRESS2 and, more recently, EUROPA studies16 have examined the effects of preventive treatment with ACE inhibitors in normotensive high-risk patients. In the HOPE study, patients with CHD, peripheral vascular disease, stroke, or diabetes (types 1 or 2) and an additional risk factor were randomly allocated to receive ramipril 10 mg daily or placebo. Patients were included irrespective of a history of hypertension, but those with blood pressure greater than 140/90 mmHg or with a specific indication for treatment with an ACE inhibitor (eg, CCF) were excluded. The 3/1 mmHg lower blood pressure in the ramipril group at the end of the study was unlikely to explain the highly significant 22% reduction in the combined endpoint of cardiovascular death, stroke or heart attack (cardiovascular death [26% reduction; ARR, 2.0%], stroke [32% reduction; ARR, 1.5%], heart attack [20% reduction; ARR, 2.2%]; P < 0.05) or the 17% decrease in total mortality (P < 0.05).1 In the PROGRESS study,2 patients with a previous history of stroke or TIA were randomly allocated to perindopril 4 mg ± indapamide 2.5 mg versus placebo, whether there was a history of hypertension or not. When given together this combination reduced the risk of recurrent stroke (fatal or non-fatal) and major vascular events in both normotensive and hypertensive patients with this background.2 There was also a significant reduction in major coronary events (26%) and the development of heart failure (26%) in these patients with underlying cerebrovascular disease.17 The magnitude of blood pressure reduction in the active treatment group was greater in the PROGRESS study (9/4 mmHg) than in the HOPE study (3/1 mmHg), making it less clear as to how much of the benefit seen in the PROGRESS study was independent of blood pressure reduction alone. The recently published EUROPA study16 looked at patients with known ischaemic heart disease, and participants were randomly allocated to receive perindopril 8 mg or placebo, independent of whether or not they had a history of hypertension. At 5 years, there was a significant 20% reduction in cardiovascular mortality, infarction and cardiac arrest in patients who received perindopril, with a blood pressure difference of 5/2 mmHg between the groups. It appears that, in patients with a history of CHD or cerebrovascular disease, treatment with a high dose ramipril- or perindopril-based regimen will improve outcomes whether or not there is a history of hypertension, and that at least some of these benefits are independent of blood pressure reduction alone. In the immediate post-infarct management of normotensive patients, a mortality benefit in the short term has also been demonstrated with β-blockers18 and ACE inhibitors (particularly in patients with associated heart failure),19 with less robust evidence for calcium channel blockers, verapamil and diltiazem.20-22 2. Patients with elevated blood pressure and a history of cardiovascular diseaseWhile epidemiological studies have established that raised blood pressure is a major risk factor for cardiovascular events in patients with a history of AMI,23 until recently there has been no systematic review or RCT that specifically examines blood pressure reduction in patients with established CHD, nor in those with peripheral vascular disease; however, the results of the HOPE, PROGRESS and EUROPA studies are applicable to patients with hypertension. In our recommendations, and those of both the JNC-7 Report24 and the National Heart Foundation,25 the benefits of blood pressure lowering in patients with CHD have been extrapolated mostly from primary prevention trials and from studies of patients after AMI.1,18-22 Evidence of event reduction exists for patients taking calcium channel blockers,20-22,26-29 diuretics and β-blockers,29-35 and ACE inhibitors.1,28,35 In patients with elevated blood pressure and a history of stroke or TIA, the evidence is strongest for the use of ACE inhibitors (ramipril 10 mg; and perindopril 4 mg when given with indapamide 2.5 mg),1,2 diuretics and β-blockers.34-38 More recently, the INVEST study39 examined patients with hypertension and known ischaemic heart disease. This study found that event rates were similar in both subjects taking a verapamil-based regimen and in those receiving atenolol-based therapy. However, to achieve target blood pressures, most patients in both study groups were taking combination therapy that also included an ACE inhibitor and thiazide diuretic. As over 50% of patients in the ALLHAT study38 had a history of atherosclerotic cardiovascular disease, the result of this study should be considered when blood pressure lowering is contemplated for such patients.38 Specifically, the results of treatment with ACE inhibitors, diuretics or calcium channel blockers were comparable. It should be noted, however, that there was an increased rate of development of diabetes mellitus in the thiazide diuretic treatment arm. In view of the impact of diabetes on cardiovascular event rates, this finding may have implications for cardiovascular disease beyond the 5-year treatment period covered by the trial. 3. Patients with dyslipidaemia and a history of cardiovascular diseaseThere is strong RCT evidence that lowering cholesterol levels decreases cardiovascular mortality and morbidity in patients who have been diagnosed with an acute coronary syndrome or myocardial infarction,40 even if cholesterol levels are normal.3,41,42 The most substantial data are from studies of simvastatin and pravastatin,3,40-42 but, recently, results of the PROVE-IT study43 suggest that intensive lipid lowering with atorvastatin 80 mg improves outcomes more than moderate lipid lowering in patients with acute coronary syndromes and cholesterol levels less than 6.2 mmol/L.43 The Heart Protection Study3 provides the most complete information of the benefits of lowering cholesterol level in a wide range of circumstances. Both men and women with total cholesterol levels greater than 3.5 mmol/L and with a history of cardiovascular disease (including those with a history of coronary disease, cerebrovascular disease, or peripheral vascular disease) achieved a significant reduction in major vascular events (P < 0.001) irrespective of the starting cholesterol level. In men with low levels of HDL cholesterol and a history of CHD, gemfibrozil significantly reduced the risk of major cardiovascular events, in the absence of an effect on LDL cholesterol level.44 In patients with diabetes and CHD, the data are strongest for the use of statins,3,40-42 but, again, in patients with low levels of HDL cholesterol gemfibrozil is efficacious.44 To date, this evidence has been derived from subgroup analyses. In RCTs, it has been shown that both pravastatin and simvastatin reduce the incidence of stroke in patients with CHD,3,41,42,45 but in those without CHD the evidence is strongest for simvastatin.3 There are no “head-to-head” outcome studies of statins versus fibrates. Recommendations for patients with diabetes without known cardiovascular disease1. Patients with diabetes and “normal” blood pressureIn patients with diabetes, “normal” blood pressure is arbitrarily defined as being less than 130/85 mmHg and “ideal” blood pressure as less than 120/80 mmHg.25 As the HOPE study1 only included patients with diabetes if they had at least one cardiovascular risk factor, treatment of low-risk patients with diabetes (ie, those who have no additional cardiovascular risk factors) with an ACE inhibitor to prevent future CHD events is not supported by current data. Observation with repeated measurement of blood pressure at least annually is recommended.25,46 2. Patients with diabetes and elevated blood pressureA systematic review of RCTs has shown that ACE inhibitors, diuretics, calcium channel blockers and β-blockers are all effective in primary prevention of cardiovascular events in patients with diabetes and hypertension.47 There is no clear evidence that any of these classes is more effective than another in event reduction,26,28 and currently drugs of all of these classes are recommended to treat blood pressure in patients with diabetes.25 Despite this, an apparent greater reduction in major cardiovascular events (including heart failure) occurring with ACE inhibitors, compared with some calcium channel blockers,48-50 has led us to list calcium channel blockers as second-line therapy. In addition to reducing cardiovascular events, ACE inhibitors have a major role in renal protection in patients with type 1 diabetes and hypertension.51 Similar protection has recently been shown with the AIIRAs irbesartan52,53 and losartan,54 including patients with type 2 diabetes and left ventricular hypertrophy.55 3. Lowering cholesterol level in patients with diabetesIn the Heart Protection Study,3,56 patients with diabetes with a total cholesterol level greater than 3.5 mmol/L had significantly fewer major vascular events (P < 0.0001) when taking simvastatin 40 mg, whether or not they had a prior history of CHD. To date, this is the largest intervention trial of statin therapy in patients with diabetes and thus should be considered the definitive trial. These data support the use of a statin for both primary and secondary prevention of major vascular events in patients with diabetes. Furthermore, three large primary prevention RCTs using lovastatin,57 gemfibrozil58 and bezafibrate59 have each shown a benefit in preventing cardiovascular events. Thus, a predominant elevation of total or LDL cholesterol levels indicates a statin is appropriate initial therapy, whereas a fibrate could be an appropriate choice in patients with low levels of HDL cholesterol and raised triglyceride levels. When treating combined hyperlipidaemia, both classes of drug may be required, but there are no outcome data from using this approach and practitioners should exercise caution in prescribing this combination. Definitive trials on lipid management in patients with diabetes (eg, the FIELD study60) are still to be published. 4. Cardiovascular prevention with other therapiesAs the HOPE study included patients with diabetes and dyslipidaemia (total cholesterol level > 5.2 mmol/L and HDL cholesterol level 0.9 mmol/L),61 the use of ramipril in addition to other therapies should be advocated in diabetic patients with dyslipidaemia or other cardiovascular risk factors. Recommendations for patients with non-diabetic renal disease1. Patients with non-diabetic renal disease and “normal” blood pressureRenal insufficiency is a well described predictor of cardiovascular outcomes.62 Hypertension in patients with renal disease is defined as blood pressure greater than 130/85 mmHg,25 although observational studies suggest that even a lower blood pressure confers an increased risk. Despite this, there is no RCT of antihypertensive therapy showing treatment benefit if blood pressure is below this threshold. Ongoing observation with repeated measurement of blood pressure every 6 months is currently recommended for normotensive patients with non-diabetic renal disease.24,25,46 2. Patients with non-diabetic renal disease and hypertensionThe benefits of treating hypertension in patients with established renal disease have largely been studied with surrogate endpoints, and the effects of lowering blood pressure on cardiovascular outcomes have not been specifically assessed. Nevertheless, patients with renal dysfunction are at high risk of CHD and it is reasonable to extrapolate from this that aggressive blood pressure lowering will confer a substantial benefit.25 Published data support the use of ACE inhibitors as first-line treatment for hypertension, with greater demonstrated efficacy in reducing proteinuria than calcium channel blockers.51 Further, in a meta-analysis of a number of clinical trials, ACE inhibitors were more effective than other agents in delaying the development of end-stage renal disease; however, it could not be determined whether this was due to the lower blood pressure achieved with ACE inhibitors or to effects independent of blood pressure.63 β-Blockers and diuretics are also recommended.24,25 If calcium channel blockers are used they should be considered as second-line therapy after ACE inhibitors.51 More recent information in this patient group has been derived from the CATS64 and COOPERATE65 studies. The CATS study showed that, although renal function deteriorated markedly after a first AMI, it was significantly preserved by taking the ACE inhibitor captopril. Patients after a first anterior-wall AMI were allocated at random to receive captopril (up to 75 mg daily) or placebo, after completion of a streptokinase infusion. Renal function determined by calculating glomerular filtration rate was found to decline by 5.5 mL/min within 1 year versus only 0.5 mL/min in the captopril group (P < 0.05). The beneficial effects of captopril were most pronounced in patients with the most compromised renal function at baseline. The COOPERATE study65 aimed to assess the effects of ACE inhibitor and AIIRA therapy, both in combination as well as monotherapy at maximal dose. Participants were randomly assigned to receive losartan 100 mg daily or trandolapril 3 mg daily, or a combination of both drugs at equivalent doses. Survival analyses were done to compare the effects of each regimen on the primary combined endpoint of time to doubling of serum creatinine concentration or end-stage renal disease on an intention-to-treat basis. Eleven per cent of patients taking the combination treatment reached the combined primary endpoint, compared with 23% of patients taking trandolapril alone (hazard ratio, 0.38; 95% CI, 0.18–0.63; P = 0.018) and 23% of patients taking losartan alone (hazard ratio, 0.40; 95% CI, 0.17–0.69; P = 0.016). Combination treatment was found to safely retard the progression of non-diabetic renal disease compared with monotherapy; however, as some patients taking combined therapy reached the combined endpoint, further research on strategies for complete management of progressive non-diabetic renal disease is needed. 3. Lowering cholesterol level in patients with non-diabetic renal diseaseSpecific trials of lipid-lowering therapy have not been conducted in patients with non-diabetic renal disease. Thresholds for intervention have been derived by consensus and recommendations for the choice of agents have been based on the lipid-lowering characteristics of specific therapies. The approach for other high-risk patientsOver the past decade, it has been recommended that the intensity of risk-factor management be governed by a patient’s absolute risk of a CHD event. However, patients with mild levels of multiple risk factors may be at high risk because of the exponential additive contribution of each risk factor,66 whereas other patients may have an overall low risk even if they have one markedly abnormal risk factor (Box 1). 1. High-risk patients with raised blood pressureA number of systematic reviews have shown a reduction in total mortality, cardiovascular death, stroke, major coronary events and CCF in patients taking β-blockers, diuretics, ACE inhibitors or calcium channel blockers.25,62,67 One unblinded RCT in 6600 people aged 70–84 years, comparing diuretics and/or β-blockers versus calcium channel blockers versus ACE inhibitors, showed no significant difference in blood pressure control or cardiovascular morbidity and mortality.68 The ALLHAT study, involving hypertensive patients with at least one other CHD risk factor, supports these findings.38,69 When the primary outcome was considered (fatal CHD or non-fatal AMI), diuretic-based therapy (chlorthalidone) was of similar efficacy to either therapy with a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril). In fact, patients taking amlodipine had an increased risk of CCF (relative risk, 1.38; 95% CI, 1.25–1.52) and patients taking lisinopril had a higher risk of combined cardiovascular disease, stroke and CCF.38 As amlodipine is a dihydropyridine calcium channel blocker, it may not be possible to extrapolate these results to the non-dihydropyridine calcium channel blockers.69 2. Lowering cholesterol level in patients at high risk of a cardiovascular eventUntil recently, there was no evidence that lowering cholesterol level reduces total mortality in non-diabetic patients without cardiovascular disease, although systematic reviews and RCTs had shown that cholesterol reduction improves cardiovascular outcomes in high-risk populations.3,57,70-72 The benefit is related to baseline risk and extent of cholesterol reduction rather than initial cholesterol level (within the range studied). The lipid-lowering arm of the ASCOT study73 demonstrated the benefits of lipid reduction for hypertensive patients with multiple cardiovascular risk factors. ASCOT examined 10 305 patients with hypertension and at least three other cardiovascular risk factors (excluding previous AMI or current angina) who had non-fasting cholesterol levels less than 6.5 mmol/L. Treatment with atorvastatin 10 mg conferred a 36% reduction in fatal CHD and non-fatal AMI compared with placebo (P = 0.0005). The benefits of lipid reduction were also evident among non-diabetic patients. A total cholesterol level greater than 5 mmol/L is the current recommended threshold for treatment in patients with associated risk factors or vascular disease.74 The approach for patients at low risk of a cardiovascular eventPatients who are not in any of the above categories are at low risk of a cardiovascular event. There is a more liberal threshold for intervention in this group in the knowledge that the treatment benefits will be smaller, but the recommendations for choice of therapy to lower blood pressure and lipid levels are identical to those in higher-risk patients. 1. Blood pressure managementWe routinely adopt a more proactive approach for monitoring blood pressure than the current guidelines, which advocate that low-risk patients whose blood pressure is considered normal by current criteria should have blood pressure measurements either every 5 years (age < 60 years) or every 1–2 years (age > 60 years).25,67 Current clinical practice would also be at variance with the guideline recommendations that drug therapy and lifestyle modification for hypertension should only be introduced in patients under 60 years if their systolic blood pressure is greater than 180 mmHg or diastolic blood pressure greater than 100 mmHg,25,67 or in those over 60 years whose systolic blood pressure is greater than 160 mmHg.27,29 Despite our personal views, we have included the current published recommendations.25 In the ANBP-2 Study,75 6083 elderly subjects aged 65–84 years with hypertension were treated with either ACE inhibitors or diuretics and compared. Although a similar number of strokes occurred in each group, ACE inhibitor therapy was associated with better cardiovascular outcomes, particularly in men.75 2. Lipid managementPatients with normal lipid levels should be assessed every 5 years until middle age and then every 1–2 years. In the absence of other risk factors triggering a lower threshold for treatment, lipid-lowering therapy with a statin should be commenced for patients with predominant hypercholesterolaemia (total cholesterol > 8.0 mmol/L or total cholesterol : HDL cholesterol ratio > 8.0),76 or with a fibrate for patients with low HDL cholesterol and high triglyceride levels.74 (At present, the reimbursement criteria of the Pharmaceutical Benefits Schedule are at variance with National Heart Foundation guidelines). The approach for patients with macro- or microalbuminuria associated with diabetes or hypertensionThe finding of microalbuminuria (urinary albumin excretion 20–200 μg/min) or macroalbuminuria (urinary albumin excretion > 200 μg/min) should prompt a search for the presence of diabetes, hypertension or renal disease. If diabetes is present, the use of ramipril is appropriate for cardiovascular risk reduction.1,61 Furthermore, there is good evidence to support the use of ACE inhibitors for renal risk reduction in normotensive patients with diabetes (type 1 or type 2) and microalbuminuria1,77 and hypertensive patients with type 2 diabetes,51 and the use of AIIRAs (irbesartan and losartan) in patients with type 2 diabetes.52-54 Other interventions1. Antiplatelet therapies (aspirin, dipyridamole or clopidogrel)Aspirin (75–150 mg/day) has been shown to have significant benefit for patients at high risk of cardiovascular disease, particularly in secondary prevention,78,79 although blood pressure should be tightly controlled to minimise the risk of haemorrhagic stroke.80-82 It must be recognised, however, that the benefits of aspirin are not clear in older patients (> 70 years) with no previous cardiovascular events who, primarily due to age, remain at high risk of cardiovascular disease. This is highlighted by the recent FDA decision not to list primary prevention of cerebrovascular disease as an indication for aspirin in the elderly and to strongly support proposals for the conduct of such trials. The risks associated with gastrointestinal and cerebral bleeding in older patients may offset any cardiovascular protection benefits. The American Diabetes Association recommends the use of aspirin for patients with diabetes over the age of 30 years,83 but there is no evidence of benefit in primary prevention in low-risk subjects.80 Alternative or additional antithrombotic therapies such as clopidogrel or dipyridamole (stroke or TIA only) may be required if aspirin is not tolerated or the patient experiences recurrent cardiovascular events while taking aspirin.84-87 It is beyond the scope of this review of cardiovascular prevention measures to focus on the management of acute coronary syndromes. However, it is important to highlight the results of a recent trial using combination antiplatelet therapy in patients with acute coronary syndromes: initiating therapy during the acute management phase in hospital was shown to have benefits up to 1 year after the initial presentation. The CURE study88 showed that patients with acute coronary syndromes who were given a loading dose of 300 mg of clopidogrel followed by ongoing treatment with 75 mg daily for 9 months, in addition to their usual therapy (including aspirin), had a 20% reduction in the combined endpoint of cardiovascular death, AMI, and stroke (ARR, 2.1%).89 Thus, many patients who leave hospital after an admission with unstable angina or non-ST elevation myocardial infarction will be receiving clopidogrel in addition to aspirin as combined antiplatelet therapy for atherothrombosis, which should be continued as long-term therapy. The CREDO study showed a 27% relative risk reduction (ARR, 3.0%) in the combined endpoint of death, AMI and stroke at 1 year with the use of clopidogrel added to conventional therapy (including aspirin) after placement of a coronary stent.89 Once again, early treatment translates into long-term preventive therapy, and thus a case can be made for the use of combination antiplatelet therapy (aspirin and clopidogrel) for preventing ischaemic events in appropriate patients. Definitive long-term trials of this combination to prevent events in patients with cardiovascular disease (but who have not presented with an acute coronary syndrome), or to avoid the need for coronary artery stenting, are currently under way. 2. AnticoagulationLong-term anticoagulation to reduce thromboembolism may be required for patients with paroxysmal or chronic atrial fibrillation, proteinuria greater than 3 g/day, and those with a history of extensive anterior infarction or severe CCF.90,91 ConclusionPrevention of cardiovascular disease: an evidence-based clinical aid 2004 is based on a review of current evidence and practice, incorporating data from RCTs, as well as recommendations from local and international guidelines. This clinical aid consolidates current evidence and recommendations into a single source and provides a reference tool for the optimal treatment of “at-risk” patients to prevent vascular events and improve clinical outcomes. 1 Categories of patients based on future risk of a cardiovascular event High-risk patients are those with: Clinically evident coronary heart disease (prior acute myocardial infarction, angina, or history of a revascularisation procedure) Clinically evident vascular disease (cerebrovascular or peripheral vascular disease) Diabetes Renal disease A risk of a future vascular event ≥ 2%–3% per year, based on an aggregate of unfavourable risk characteristics* Low-risk patients are those with: A risk of a future vascular event < 2%–3% per year* * Determined using a calculation of the 5-year risk of any cardiovascular event and death, from a validated absolute-risk calculator such as the Framingham Heart Study Prediction Score Sheets or, in the case of type 2 diabetes, the UK Prospective Diabetes Study risk calculator (www.dtu.ox.ac.uk/index.html?maindoc=/riskengine/). 2 Competing interests Name Consultant fees Honoraria/fees for service Advisory/Steering Committee fees Investigator-initiated research grants Travel assistance Dr John V Amarena BMS, Boehringer Ingelheim, Novartis, Sanofi Abbott, Aventis, BMS, MSD, Servier, Solvay Aventis, BMS, Sanofi Boehringer Ingelheim, Pfizer, Sanofi Dr John F Beltame Alphapharm, Aventis, Bayer, BMS, MSD, Pfizer, Roche, Sanofi, Servier Aventis, BMS, Pfizer, Solvay Prof Stephen Colagiuri MSD, Novo Nordisk, Roche, Servier Member of MSD steering committee — unpaid Dr Greg W Conner Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Dr Greg R Fulcher Aventis, BMS, MSD, Novo Nordisk, Sanofi, Eli Lilly Aventis, GSK, MSD, Novo Nordisk, Sanofi, Aventis, MSD Prof Richard E Gilbert Aventis, AZ, BMS, MSD BMS AZ, Servier Prof Graeme Hankey BMS, Sanofi Aventis, BMS, MSD, Pfizer, Sanofi BMS, Pfizer, Sanofi Assoc Prof Anthony C Keech Laboratoires Fournier, MSD (contribution to department) BMS, Laboratoires Fournier, MSD Invited lectures only Prof Brian R McAvoy Aventis Prof Carol A Pollock Aventis, Sanofi, Servier BMS Prof Malcolm J West Aventis, BMS, MSD Aventis, BMS, MSD BMS, MSD BMS Aventis, BMS, MSD Abbott = Abbott Australasia; Aventis = Aventis Pharma; AZ = AstraZeneca; BMS = Bristol-Myers Squibb; GSK = GlaxoSmithKline; MSD = Merck Sharpe & Dohme/Amrad; Sanofi = Sanofi-Synthelabo

Practical Implementation Taskforce for the Prevention of Cardiovascular Disease

Evidence-based health policy: Problems and possibilities. Vivian Lin, Brendan Gibson (editors). Melbourne: Oxford University Press, 2003 (xxvi + 374 pp). ISBN 0 19 551551. I really enjoyed this book. It is well constructed, informative, intelligently written, and for the most part, intelligible. The editors have assembled an eclectic and informed group of authors who shed considerable light on the problems of underpinning policy development with “evidence”. Despite the difficulties inherent in defining what is meant by “policy”, and what constitutes “evidence”, the themes come through clearly and the lessons are many. For those of a scientific bent, the issue would seem straightforward enough. You conduct research, come to a conclusion on the results of that research, and frame your policy and subsequent actions accordingly. But that simplified view of the world doesn’t often hold up. Interpretations of particular data by knowledgeable, rational people may differ widely, the data themselves may directly conflict, and the sum total of information may be incomplete and inadequate for generating good policy. Those people whose working lives have been dedicated to policy development see greater complexity in the influences that shape policy, and have a different view of what constitutes “evidence”. A rational policy may be in part founded on “scientific” evidence, but the more important influences might include the political setting, people’s expectations and their view of what works for them, and the financial constraints. A technically correct policy may founder on the rocks of cultural opposition or political reality. And then there are those with competing interests who interpret evidence for their own ends, and those who assemble the results of research after the event to justify a policy position that had already been taken. Such misuse of evidence does nothing to enhance the common good. The book provides various case studies that provide excellent examples of how evidence may be applied or misapplied. Health policy, a “strife of competing interests”, may also be thought of as “islands of excellence in an ocean of business as usual”. However, I take heart from this volume that evidence of effectiveness can be, and is, increasingly embraced in the formulation of health policy, as it is in healthcare. The possibilities may eventually overcome the problems. Richard A SmallwoodProfessor of Medicine University of Melbourne, VIC

Richard A Smallwood

Children of prisoners During 2001, about 14 500 children younger than 16 years of age in NSW experienced having a parent imprisoned at least once that year, say Sydney researchers. Further, about 60 000 children in NSW had experienced such an event during their lifetime — 4.3% of all children, and 20.1% of all Indigenous children, in the state. The researchers' estimate was derived from a cross-sectional survey of more than 800 inmates randomly selected from each of the state’s 29 prisons, taking into account high recidivism rates and a considerable increase in Australia’s prison populations over time. They say we need practical policies to protect these vulnerable children from the chain of adversity they will otherwise face in their lives. Aust N Z J Public Health 2004; 28: 339-343 Driving blind? Sydney researchers suggest that doctors are not formally assessing their patients' visual function in everyday clinical practice and/or are gaining incorrect impressions of patients' abilities. They were commenting on some of their findings in a study of 111 patients recruited prior to cataract surgery, which examined various patient-centred outcomes. The researchers found that 10 of the 43 patients who were driving motor vehicles before surgery were doing so illegally, with the patients' best eye’s visual acuity worse than 6/12. After surgery, 57 study patients reported driving — all legally. Clin Exp Ophthalmol 2004; 32: 388-392 Peak performance International experts warn that it is premature for adventurers to try out sildenafil (Viagra) (now known to mimic the features of a selective pulmonary vasodilator), as a performance-enhancing drug when mountaineering or hiking.1 Their caution accompanies the report of a small but impressive placebo-controlled cross-over study conducted in 14 healthy volunteers at the high altitude Mount Everest Base Camp. The study found that a single dose of 50 mg sildenafil led to several beneficial effects, including increased exercise capacity. However, sildenafil can cause headache, one of the symptoms of acute mountain sickness, and, the experts say, we do not yet understand the mechanisms responsible for the effects described. 1. Ann Intern Med 2004; 141: 233-235 2. Ann Intern Med 2004; 141: 169-177 "Brief" relief In managing osteoarthritis, topical therapy with NSAIDs is best used for short periods (up to two weeks) during flare-ups, say UK authors. Their advice follows a meta-analysis of 13 randomised controlled trials comparing topical NSAIDs with placebo or oral NSAIDs, which found that topical NSAIDs were superior to placebo in relieving pain due to osteoarthritis in only the first two weeks (of up to four weeks) of treatment. However, the meta-analysis also suggested that, rather than being a class effect, this beneficial effect could depend on the specific NSAID used. 1. BMJ 2004; 329: 304-305 2. BMJ 2004; 329: 324-326 Fair’s fair US editorialists say that the medical profession should be mortified that no other profession in their country exhibits greater gender disparities when it comes to position and pay.1 They were commenting on a US national survey of 1814 full-time faculty members of 24 medical schools in the mid-1990s, which found that female faculty members neither advanced as rapidly nor were compensated as well as male colleagues who were professionally similar (eg, in terms of total career publications, hours worked per week, type of department).2 Further, the differences in pay became greater with increasing seniority. The female editorialists said that, in the past, they had learnt that their own salaries were in the lowest 5% for their rank after reviewing grant applications and following up a colleague’s tip-off about a relevant US report about salary ranges for academic faculty. 1. Ann Intern Med 2004; 141: 238-240 2. Ann Intern Med 2004; 141: 205-212 Columbine’s legacy According to surveys of US high school students, the USA may well achieve two of its national health objectives for 2010: physical fighting among adolescents is down from 42.5% in 1991 to 33.0% in 2003 (2010 target, <32%), and weapon carrying on school property is down from 11.8% in 1993 to 6.1% in 2003 (2010 target, < 4.9%). However, significantly more children are now reporting not going to school because of safety concerns (either at school or on the way to or from school), up from 4.4% in 1993 to 5.4% in 2003. High-profile, school-associated, multivictim homicides in the 1990s are thought to be responsible for a heightened sense of vulnerability among students. MMWR Morb Mortal Wkly Rep 2004; 53: 651-655 Dr Ann Gregory, MJA

Ann Gregory

Med J Aust 2004; 181 (6 Suppl).